MAGE-n与CD80融合基因肿瘤疫苗的构建及体内抑瘤效应的研究
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摘要
长久以来,恶性肿瘤一直严重威胁着人类的健康和生命,传统的治疗方法不尽如人意。免疫治疗通过提高肿瘤的免疫原性,诱导机体产生特异性的抗肿瘤免疫反应,达到治疗肿瘤的目的,是一种变被动为主动的生物治疗方法。在研究者的共同努力下,有关肿瘤免疫治疗的基础和临床应用研究已取得一定的进展,在肿瘤的防治上也显示出一定的效果。但是人们仍在不断地探索和尝试,力图研制出高效、广谱的肿瘤疫苗,以挽救更多肿瘤患者的生命,给人们带来新的希望。
MAGE-n是由我室首次报道的,克隆自肝细胞癌细胞系的,MAGE家族基因的新成员(GeneBank登录号AF443295),它与MAGE-A亚家族基因有较高的同源性。MAGE-n分子上存在可诱导MAGE-n特异性CTL的抗原表位,而且在体内能产生特异性的抗肝癌免疫效应。CD80是一种共刺激分子,在T细胞的活化和抗肿瘤免疫反应中起着重要作用。CpG作为一种免疫佐剂,可以诱发机体产生多种免疫学效应。本研究构建MAGE-n与CD80融合基因肿瘤疫苗,以CpG为佐剂,研究其对小鼠细胞免疫及体液免疫的影响,并利用小鼠肿瘤模型观察对肿瘤的防治作用。
1.MAGE-n基因的克隆、原核表达、抗血清的制备及其在不同组织中的表达
Tumor is always a big threat against people's health and life, and the available protocols are far from satisfaction. Tumor biological therapies, which can elicit antigen-specific antitumor immunity and play an important role in prevention and therapy of tumor, are regarded as the most attractive method. Scientists have made great progresss in basal and clinical research of tumor biological therapies. However people are still exploring and trying to find a more efficient, more broad-spectrum tumor vaccine to save more patients' life, which will bring a hope for humankind.MAGE-n is a new member of MAGE gene family, which was firstly reported by our research group (GeneBank, Locus No.AF443295), and cloned from Hepatocellular carcinoma cell line (HCCC). It is highly homologous to MAGE-A subfamily genes. The CTL epitopes of MAGE-n were identified and proved to elicit MAGE-n-specific CTLs, and to be a potential target of specific immunotherapy for HLA-A2+ HCC patients in the future. CD80 is one of costimulating factor, which plays a key role in T cells activation and antitumor immunity. As a kind of adjuvant, CpG-ODN can induce great immunological effects. In our research, the MAGE-n and CD80 fusion DNA vaccine was constructed. Conjucted with CpG-ODN adjuvant, the humoral- and cellular-activating effects of the fusion DNA vaccine were measured, and the therapeutic and protective effects of the vaccines against established tumor expressing MAGE-n were investigated.
1: Cloning, Prokaryotic Expression of Human MAGE-n, Preparation of Antiserum, and Expression of MAGE-n in Different TissuesObjective: To construct MAGE-n prokaryotic expression plasmid. To express the MAGE-n gene in E. coli, and to purify the protein. To obtain the anti-MAGE-n polyclonal antibody. To investigate the expression of MAGE-n in different tissues. Methods: The full-length ORF of MAEG-n gene was amplified by PCR from HHCC. Antigenicity of MAGE-n was analyzed by biological software. 300 bp segment of MAGE-n gene was amplified by PCR. The expression plasmid pGEX-MAGE-n was constructed, the DH5a containing the plasmid was induced by IPTG and the protein was purified with GSTrap FF column. Antiserum against MAGE-n was prepared by immunizing rabbit with the purified recombinant MAGE-n protein conjucted with Freund's adjuvant. The anti-MAGE-n antiserum was purified through (NH4)2SO4 precipitation and CNBr-Activated Sephrose 4B chromatography, which was identified by agar gel precipitation, ELISA, and Western blot. The immunohisto-chemical analysis was used to detected the expression of MAGE-n in tumor, infiammantion and normal tissues. Results: The MAGE-n gene was cloned from HHCC, and the sequence was identical with that reported in GeneBank. The 100 aa (88-187 aa) segment of MAGE-n had a high antigenicity and specificity. The pGEX-MAGE-n plasmid was successfully constructed and the DH5a containing the plasmid could express a 40 kD protein whose purity was 82%. High titer antiserum against MAGE-n was obtained in immunized rabbits and the specificity to MAGE-n was increased by affinity chromatography. Immunocytochemical analysis with this antibody showed that MAGE-n expressed in cytoplasm. MAGE-n expressed in malignant tumor tissues and HHCC, 7402 cell lines, and not expressed in benign tumor, infiammantion, normal tissues and HepG2, 9204, 7721 cell lines. Conclusion: The protein of human MAGE-n segment was expressed and purified firstly. A high titer, specific rabbit antiserum against MAGE-n was prepared successfully. The expression of MAGE-n in different tissues was measured by the method of immunohistochemistry, which was identical with that of MAGE-A genes. The study prepared the materials for the further research of the MAGE-n as a promising candidate for tumor vaccine.
2: The Constructions and Expression of MAGE-n and CD80 Fusion PlasmidObjective: To construct CD80, MAGE-n and MAGE-n/CD80 fusion plasmid and investigate their expression in vivo and vitro. To establish the B16 cell stably expressing MAGE-n. Methods: The eukaryotic expression plasmids pcDNA3.1+-CD80 and pcDNA3.1+-CD80/IRES/MAGE-n were constructed, and the later was transfected to NIH3T3 through Lipofectamine? 2000. By the method of FCM and immunocytochemistry, the expression of MAGE-n and CD80 were detected in transfected NIH3T3. Recombinant plasmid and Lipofectamine were injected on the leg of C57BL/6 mouse. Through semi-quantification RT-PCR and immunohistochemistry, MAGE-n and CD80 were proved to express in muscular tissues. The pcDNA3.1+-MAGE-n plasmid was constructed, then transfected into the mouse melanoma B16 cells under mediation of Lipofectamine. The positive clones were selected by G418. MAGE-n DNA, mRNA and protein in positive clones were detected by PCR, RT-PCR, Western blot and immunocytochemistry respectively. Results: pcDNA3.1+-CD80 and pcDNA3.1+-CD80/IRES/MAGE-n plasmids were constructed successfully. After transfection, CD80 was tested to express on the membrane of NIH3T3, and MAGE-n express in the plasm of NIH3T3. The MAGE-n positive materials were detected in the plasm of transfected NIH3T3. In the muscular tissues injected with the recombinant plasmid, MAGE-n and CD80 mRNA were detected by RT-PCR. In the plasm of muscular cells MAGE-n protein was detected by immunohistochemistry. The pcDNA3.1+- MAGE-n plasmid was constructed and transfected into B16 cells successfully. MAGE-n DNA, mRNA and protein in positive clones were detected respecttively. Conclusion: The coexpression plasmid pcDNA3.1+-CD80/IRES/MAGE-n was constructed successfully. Both MAGE-n and CD80 were tested to express in vivo and vitro. The B16-MAGE-n cell line stably expressing MAGE-n was obtained. These results lay a foundation for the research on antitumor effects of MAGE-n/CD80 fusion DNA vaccine.3: The Antitumor Effects of MAGE-n/CD80 Fusion DNA VaccineObjective: To evaluate the immunological effects in vivo, and protective and therapeutic effects of MAGE-n/CD80 fusion DNA vaccine on tumor.
MAGE-n是由我室首次报道的,克隆自肝细胞癌细胞系的,MAGE家族基因的新成员(GeneBank登录号AF443295),它与MAGE-A亚家族基因有较高的同源性。MAGE-n分子上存在可诱导MAGE-n特异性CTL的抗原表位,而且在体内能产生特异性的抗肝癌免疫效应。CD80是一种共刺激分子,在T细胞的活化和抗肿瘤免疫反应中起着重要作用。CpG作为一种免疫佐剂,可以诱发机体产生多种免疫学效应。本研究构建MAGE-n与CD80融合基因肿瘤疫苗,以CpG为佐剂,研究其对小鼠细胞免疫及体液免疫的影响,并利用小鼠肿瘤模型观察对肿瘤的防治作用。
1.MAGE-n基因的克隆、原核表达、抗血清的制备及其在不同组织中的表达
Tumor is always a big threat against people's health and life, and the available protocols are far from satisfaction. Tumor biological therapies, which can elicit antigen-specific antitumor immunity and play an important role in prevention and therapy of tumor, are regarded as the most attractive method. Scientists have made great progresss in basal and clinical research of tumor biological therapies. However people are still exploring and trying to find a more efficient, more broad-spectrum tumor vaccine to save more patients' life, which will bring a hope for humankind.MAGE-n is a new member of MAGE gene family, which was firstly reported by our research group (GeneBank, Locus No.AF443295), and cloned from Hepatocellular carcinoma cell line (HCCC). It is highly homologous to MAGE-A subfamily genes. The CTL epitopes of MAGE-n were identified and proved to elicit MAGE-n-specific CTLs, and to be a potential target of specific immunotherapy for HLA-A2+ HCC patients in the future. CD80 is one of costimulating factor, which plays a key role in T cells activation and antitumor immunity. As a kind of adjuvant, CpG-ODN can induce great immunological effects. In our research, the MAGE-n and CD80 fusion DNA vaccine was constructed. Conjucted with CpG-ODN adjuvant, the humoral- and cellular-activating effects of the fusion DNA vaccine were measured, and the therapeutic and protective effects of the vaccines against established tumor expressing MAGE-n were investigated.
1: Cloning, Prokaryotic Expression of Human MAGE-n, Preparation of Antiserum, and Expression of MAGE-n in Different TissuesObjective: To construct MAGE-n prokaryotic expression plasmid. To express the MAGE-n gene in E. coli, and to purify the protein. To obtain the anti-MAGE-n polyclonal antibody. To investigate the expression of MAGE-n in different tissues. Methods: The full-length ORF of MAEG-n gene was amplified by PCR from HHCC. Antigenicity of MAGE-n was analyzed by biological software. 300 bp segment of MAGE-n gene was amplified by PCR. The expression plasmid pGEX-MAGE-n was constructed, the DH5a containing the plasmid was induced by IPTG and the protein was purified with GSTrap FF column. Antiserum against MAGE-n was prepared by immunizing rabbit with the purified recombinant MAGE-n protein conjucted with Freund's adjuvant. The anti-MAGE-n antiserum was purified through (NH4)2SO4 precipitation and CNBr-Activated Sephrose 4B chromatography, which was identified by agar gel precipitation, ELISA, and Western blot. The immunohisto-chemical analysis was used to detected the expression of MAGE-n in tumor, infiammantion and normal tissues. Results: The MAGE-n gene was cloned from HHCC, and the sequence was identical with that reported in GeneBank. The 100 aa (88-187 aa) segment of MAGE-n had a high antigenicity and specificity. The pGEX-MAGE-n plasmid was successfully constructed and the DH5a containing the plasmid could express a 40 kD protein whose purity was 82%. High titer antiserum against MAGE-n was obtained in immunized rabbits and the specificity to MAGE-n was increased by affinity chromatography. Immunocytochemical analysis with this antibody showed that MAGE-n expressed in cytoplasm. MAGE-n expressed in malignant tumor tissues and HHCC, 7402 cell lines, and not expressed in benign tumor, infiammantion, normal tissues and HepG2, 9204, 7721 cell lines. Conclusion: The protein of human MAGE-n segment was expressed and purified firstly. A high titer, specific rabbit antiserum against MAGE-n was prepared successfully. The expression of MAGE-n in different tissues was measured by the method of immunohistochemistry, which was identical with that of MAGE-A genes. The study prepared the materials for the further research of the MAGE-n as a promising candidate for tumor vaccine.
2: The Constructions and Expression of MAGE-n and CD80 Fusion PlasmidObjective: To construct CD80, MAGE-n and MAGE-n/CD80 fusion plasmid and investigate their expression in vivo and vitro. To establish the B16 cell stably expressing MAGE-n. Methods: The eukaryotic expression plasmids pcDNA3.1+-CD80 and pcDNA3.1+-CD80/IRES/MAGE-n were constructed, and the later was transfected to NIH3T3 through Lipofectamine? 2000. By the method of FCM and immunocytochemistry, the expression of MAGE-n and CD80 were detected in transfected NIH3T3. Recombinant plasmid and Lipofectamine were injected on the leg of C57BL/6 mouse. Through semi-quantification RT-PCR and immunohistochemistry, MAGE-n and CD80 were proved to express in muscular tissues. The pcDNA3.1+-MAGE-n plasmid was constructed, then transfected into the mouse melanoma B16 cells under mediation of Lipofectamine. The positive clones were selected by G418. MAGE-n DNA, mRNA and protein in positive clones were detected by PCR, RT-PCR, Western blot and immunocytochemistry respectively. Results: pcDNA3.1+-CD80 and pcDNA3.1+-CD80/IRES/MAGE-n plasmids were constructed successfully. After transfection, CD80 was tested to express on the membrane of NIH3T3, and MAGE-n express in the plasm of NIH3T3. The MAGE-n positive materials were detected in the plasm of transfected NIH3T3. In the muscular tissues injected with the recombinant plasmid, MAGE-n and CD80 mRNA were detected by RT-PCR. In the plasm of muscular cells MAGE-n protein was detected by immunohistochemistry. The pcDNA3.1+- MAGE-n plasmid was constructed and transfected into B16 cells successfully. MAGE-n DNA, mRNA and protein in positive clones were detected respecttively. Conclusion: The coexpression plasmid pcDNA3.1+-CD80/IRES/MAGE-n was constructed successfully. Both MAGE-n and CD80 were tested to express in vivo and vitro. The B16-MAGE-n cell line stably expressing MAGE-n was obtained. These results lay a foundation for the research on antitumor effects of MAGE-n/CD80 fusion DNA vaccine.3: The Antitumor Effects of MAGE-n/CD80 Fusion DNA VaccineObjective: To evaluate the immunological effects in vivo, and protective and therapeutic effects of MAGE-n/CD80 fusion DNA vaccine on tumor.
引文
[1] Rosenberg SA. New opportunities for the development of cancer immunotherapies. Cancer JS ci Am, 1998, 4(suppl.1)S: 1-4
[2] Gillespie AM, Coleman RE. The potential of melanoma antigen expression in cancer therapy. Cancer Treat Rev, 1999, 25(4): 219-227
[3] 龙振洲.医学免疫学.第二版.北京:人民卫生出版社,1996,136
[4] Schlom J, Hodge JW. The diversity of T-cell co-stimulation in the induction of antitumor immunity. Immunol Rev, 1999, 170:73-84
[5] 金伯泉.细胞和分子免疫学.第二版.北京:科学出版社,2001,417-418
[6] Schuurhuis DH, Ioan-Facsinay A, Nagelkerken B, van Schip JJ, Sedlik C, Melief CJ, Verbeek JS, Ossendorp F. Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CDS+ CTL responses in vivo. J Immunol, 2002, 168(5): 2240-2246
[7] Belz GT, Carbone FR, Heath WR. Cross-presentation of antigens by dendritic cells. Crit Rev Immunol, 2002, 22(5-6): 439-448
[8] Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med, 1998, 188(12): 2357-2368
[9] Zeng G, Wang X, Robbins PF, Rosenberg SA, Wang RF. CD4(+) T cell recognition of MHC class Ⅱ-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: association with NY-ESO-1 antibody production. Proc Natl Acad Sci USA, 2001, 98(7): 3964-3969
[10] Adris S, Chuluyan E, Bravo A, Berenstein M, Klein S, Jasnis M, Carbone C, Chernajovsky Y, Podhajcer OL. Mice vaccination with interleukin 12-transduced colon cancer cells potentiates rejection of syngeneic non-organ-related tumor cells. Cancer Res, 2000, 60(23): 6696-6703
[11] 宫恩聪,丁彦青,黄高昇.大学病理学.北京:高等教育出版社,2001,130
[12] Boon T, van Baren N. Immunosurveillance against cancer and immunotherapy-synergy or antagonism? N Engl J Med, 2003, 348(3): 252-254
[13] Ochsenbein AF. Principles of tumor immunosurveillance and implications for immunotherapy. Cancer Gene Ther, 2002, 9(12): 1043-1055
[14] Gatti RA, Good TA. Occurrence of malignancy in immunodeficiency diseases. A literature review. Cancer, 1971, 28(1): 89-98
[15] Halliday GM, Le S. Transforming growth factor-beta produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin. Int Immunol, 2001, 13(9): 1147-1154
[16] Riker A, Cormier J, Panelli M, Kammula U, Wang E, Abati A, Fetsch P, Lee KH, Steinberg S, Rosenberg S, Marincola F. Immune selection after antigen-specific immunotherapy of melanoma. Surgery, 1999, 126(2): 112-120
[17] Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, Lopez-Botet M, Duggan-Keen M, Stern PL. Implications for immunosurveillance of altered HLA class Ⅰ phenotypes in human tumours. Immunol Today, 1997, 18(2): 89-95
[18] Youngchun B, Jianqiong Z, Zehui H. Association of HLA class Ⅰ antigen expression in human hepatocellar carcinoma with improved prognosis. Tissue Antigens, 2002, 59 (Suppl 2): 105-106
[19] Real LM, Jimenez P, Canton J, Kirkin A, Garcia A, Abril E, Zeuthen J, Ruiz-Cabello F, Garrido F. In vivo and in vitro generation of a new altered HLA phenotype in melanoma-tumour-cell variants expressing a single HLA-class-I allele. Int J Cancer, 1998, 75(2): 317-323
[20] Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Scienc, 1990, 248(4961): 1349-1356
[21] Li W, Rosenzweig A, Huber BT. Differential T-cell activation by B7-1 expression. Immunology, 2003, 109(3): 336-342
[22] Rogers NJ, Jackson IM, Jordan WJ, Hawadle MA, Dorling A, Lechler RI. Cross-species costimulation: relative contributions of CD80, CD86, and CD40. Transplantation,2003, 75(12): 2068-2076
[23] Salazar-Onfray F. Interleukin-10: a cytokine used by tumors to escape immunosur-veillance. Med Oncol, 1999, 16(2): 86-94
[24] Ke Y, Kapp LM, Kapp JA. Inhibition of tumor rejection by gammadelta T cells and IL-10. Cell Immunol, 2003,221(2): 107-114
[25] Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol, 2003, 33(5): 1205-1214
[26] Chen W, Frank ME, Jin W, Wahl SM. TGF-P released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity, 2001, 14(6): 715-725
[27] Ebert EC. Inhibitory effects of transforming growth factor-beta (TGF-beta) on certain functions of intraepithelial lymphocytes. Clin Exp Immunol, 1999, 115(3): 415-420
[28] Ristimaki A, Honkanen N, Jankala H, et al. Expression of cycleocoxygenase 2 in human gastric carcinoma. Cancer Res, 1997, 57(7): 1276-1280
[29] Eisengart CA, Mestre JR, Naama HA, Mackrell PJ, Rivadeneira DE, Murphy EM, Stapleton PP, Daly JM. Prostaglandins regulate melanoma-induced cytokine production in macrophages. Cell Immunol, 2000,204(2): 143-149
[30] Toi M, Taniguchi T, Yamamoto Y, Kurisaki T, Suzuki H, Tominaga T. Clinical significance of the determination of angiogenic factors. Eur J Cancer, 1996, 32A(14): 25 13-2539
[31] Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, Gabrilovich DI. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol, 1998, 160(3): 1224-1232
[32] Saito H, Tsujitani S, Ikeguchi M, Maeta M, Kaibara N. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer, 1998, 78(12): 1573-1577
[33] Voorzanger N, Touitou R, Garcia E, Delecluse HJ, Rousset F, Joab I, Favrot MC, Blay JY. Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin's lymphoma cells and act as cooperative growth factors. Cancer Res, 1996, 56(23): 5499-5505
[34] Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Pal-ucka K. Immunobiology of dendritic Cells. Annu Rev Immunol, 2000, 18: 767-811
[35] Carbone JE, Ohm DP. Immune dysfunction in cancer patients. Oncology (Huntingt),2002, 16(1 Suppl 1): 11-18
[36] Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kava-naugh D, Carbone DP. Production of vascular endothelial growth factor by tumors inhi- bits the functional maturation of dendritic cells. Nat Med, 1996, 2(10): 1096-1103
[37] Lespagnard L, Gancberg D, Rouas G, Leclercq G, de Saint-Aubain Somerhausen N, Di Leo A, Piccart M, Verhest A, Larsimont D. Tumor-infiltrating dendritic cells in adenocarcinomas of the breast: a study of 143 neoplasms with a correlation to usual prognostic factors and to clinical outcome. Int J Cancer, 1999, 84(3): 309-314
[38] Chaux P, Favre N, Martin M, Martin F. Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression in rats. Int J Cancer, 1997, 72(4): 619-624
[39] Zhu Q, Deng CS. Apoptosis of lymphocytes induced by Fas/FasL of colon cancer cells. Ai Zheng, 2002, 21(3): 272-275
[40] Rabinowich H, Reichert TE, Kashii Y, Gastman BR, Bell MC, Whiteside TL. Lymphocyte apoptosis induced by Fas ligand-expressing ovarian carcinoma cells. Implications for altered expression of T cell receptor in tumor-associated lymphocytes. J Clin Invest, 1998, 101(11): 2579-2588
[41] Cappello P, Novelli F, Forni G, Giovarelli M. Death receptor ligands in tumors. J Immunother, 2002, 25(1): 1-15
[42] Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Kayagaki N, Yagita H, Okumura K. Critical role for tumor necrosis factor-related apoptosis-induced ligand in immune surveillance against tumor development. J Exp Med, 2002, 195(2): 161-169
[43] Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev, 2001, 8(182): 18-32
[44] Wiemann B, Statues CO. Coley's toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther, 1994, 64(3): 529-564
[45] Hanna MG Jr, Hoover HC Jr, Vermorken JB, Harris JE, Pinedo HM. Adjuvant active specific immunotherapy of stage Ⅱ and stage Ⅲ trials colon cancer with an autologous tumor cell vaccine: first randomized phase Ⅱ trials show promise. Vaccine, 2001, 19 (17-19): 2576-2582
[46] Morton DL, Foshag LJ, Hoon DS, Nizze JA, Famatiga E, Wanek LA, Chang C, Davtyan DG, Gupta RK, Elashoff R, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg, 1992, 216 (4): 463-482
[47] Thomas MC, Greten TF, Pardoll DM, Jaffee EM. Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine. Hum Gene Ther, 1998, 9(6): 835-843
[48] Yang S, Darrow TL, Seigler HF. Generation of primary tumor-specific cytotoxic T lymphocytes from autoiogous and human lymphocyte antigen class Ⅰ-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells. Cancer Res, 1997, 57(8): 1561-1568
[49] Mullen CA, Petropoulos D, Lowe RM. Treatment of microscopic pulmonary metastases with recombinant autologous tumor vaccine expressing interleukin 6 and Escherichia coli cytosine deaminase suicide genes. Cancer Res, 1996, 56 (16): 1361-1366
[50] Willimsky G, Blankenstein T. Interleukin-7/B7.1-encoding adenoviruses induce rejection of transplanted but not nontransplanted tumors. Cancer Res, 2000, 60: 685
[51] 魏于全.抗肿瘤自身免疫反应与异种细胞疫苗研究进展.郭亚军主编.细胞生物学与肿瘤免疫学.北京:军事医学科学出版社,2000,208-218
[52] Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature, 1998 Mar 19, 392(6673): 245-252
[53] Nestle FO, Banchereau J, Hart D. Dendritic cells: On the move from bench to bedside. Nat Med, 2001, 7(7): 761-765
[54] Guo Y, Wu M, Chen H, Wang X, Liu G, Li G, Ma J, Sy MS. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science, 1994,263 (5146):518-520
[55] Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med, 1998,4(3): 328-332
[56] Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W. Induction of cy-totoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood, 2000, 96(9): 3102-3108
[57] Nikitina EY, Chada S, Muro-Cacho C, Fang B, Zhang R, Roth JA, Gabrilovich DI. An effective immunization and cancer treatment with activated dendritic cells transduced with full-length wild-type p53. Gene Ther, 2002, 9 (5): 345-352
[58] Specht JM, Wang G, Do MT, Lam JS, Royal RE, Reeves ME, Rosenberg SA, Hwu P. Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases. J Exp Med, 1997, 186(8): 1213-1221
[59] Song W, Kong HL, Carpenter H, Torii H, Granstein R, Rafii S, Moore MA, Crystal RG. Dendritic cells genetically modified with a adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity. J Exp Med, 1997, 186(8): 1247-1256
[60] Xia DJ, Zhang WP, Zheng S, Wang J, Pan JP, Wang Q, Zhang LH, Hamada H, Cao X. Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gpl00. Gene Ther, 2002, 9(9): 592-601
[61] Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH. Regression of human metastatic renal cell carcinoma after vaccination with tumor celldendritic cell hybrids. Nat Med, 2000, 6(3): 332-336
[62] Wang J, Saffold S, Cao X, Krauss J, Chen W. Eliciting T cell immunity against poorly immunogenic tumor by immunization with dendritic cell-tumor fusion vaccines. J Im munol, 1998, 161(10): 5516-5524
[63] Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nature Med, 1997, 3(5): 558-561
[64] Lindner M, Schirrmacher V. Tumor cell-dendritic cell fusion for cancer immunothe-rapy: comparision of therpeutic efficiency of polyethylen-glycol versus electro-fusion protocols. Eur J Clin Invest, 2002, 32: 207-217
[65] Celluzzi CM, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD Jr. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity. J Exp Med, 1996, 183(1): 283-287
[66] Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL. Direct gene transfer into mouse muscle in vivo. Science, 1990, 247(4949 Pt 1): 1465-1468
[67] Park JH, Kim CJ, Lee JH, Shin SH, Chung GH, Jang YS. Effective immunotherapy of cancer by DNA vaccination. Mol Cella, 1999, 9(4): 384-391
[68] Guo C, Ding J, Yu Z, Han Q, Meng F, Liu N, Fan D. Development of oral DNA vaccine based on MG(7)-Ag mimotope of gastric cancer. Zhonghua Zhong Liu Za Zhi, 2002,24(2): 110-113
[69] Walsh P, Gonzalez R, Dow S, Elmslie R, Potter T, Glode LM, Baron AE, Balmer C, Easterday K, Allen J, Rosse P. A phase I study using direct combination DNA injections for the immunotherapy of metastatic melanoma. Trial. Hum Gene Ther, 2000, 11 (9): 1355-1368
[70] Mincheff M, Tchakarov S, Zoubak S, Loukinov D, Botev C, Altankova I, Georgiev G, Petrov S, Meryman HT. Naked DNA and adenoviral immunizations for immunotherapy of prostate cancer: a phase I/II clinical trial. Eur Urol, 2000, 38 (2): 208-217
[71] Haupt K, Roggendorf M, Mann K. The potential of DNA vaccination against tumor-associated antigens for antitumor therapy. Exp Biol Med, 2002, 227 (4): 227-237
[72] Marshall JL, Hoyer RJ, Toomey MA, Faraguna K, Chang P, Richmond E, Pedicano JE, Gehan E, Peck RA, Arlen P, Tsang KY, Schlom J. Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol, 2000, 18(23): 3964-3973
[73] Perambakam S, Xue BH, Sosman JA, Peace DJ. Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer. Cancer Immunol Immunother, 2002, 51(5): 263-270
[74] Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE 3 and pre sented by HLA Al.Int J Cancer, 1999, 80(2): 219-230
[75] Jager E, Jager D , Knuth A . CTL-defined cancer vaccines: Perspectives for active immunotherapeutic interventions in minimal resdiual disease. Cancer and Metast Rev, 1999, 18:143-150
[76] Kim DK, Kim JH, Kim YT, Kim JW, Ioannides CG.The comparison of cytotoxic T- lymphocyte effects of dendritic cells stimulated by the folate binding protein peptide cultured with IL-15 and IL-2 in solid tumor. Yonsei Med J, 2002,43(6): 691-700
[77] Tamura Y, Peng P, Liu K, Daou M, Srivastava PK. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science, 1997, 278(5335):117-119
[78] Bhattacharya-Chatterjee M, Chatterjee SK, Foon KA. Anti-idiotype antibody vaccine therapy for cancer. Expert Opin Biol Ther, 2002, 2(8): 869-881
[79] Alfonso M, Diaz A, Hernandez AM, Perez A, Rodriguez E, Bitton R, Perez R, Vazquez AM. An anti-idiotype vaccine elicits a specific response to N-gly-colyl sialic acid residues of glycoconjugates in melanoma patients. J Immunol, 2002, 168(5): 2523-2529
[80] Pervin S, Chakraborty M, Bhattacharya-Chatterjee M, Zeytin H, Foon KA, Chatterjee SK. Induction of antitumor immunity by an anti-idiotype antibody mimicking carci- noembryonic antigen. Cancer Res, 1997, 57 (4): 728-734
[81] Dillman RO. Monoclonal antigodies in the treatment of malignancy: basic concepts and recent developments. Cancer Invest, 2001, 19(8): 833-841
[82] Ligibel JA, Winer EP. Trastuzumab/chemotherapy combinations in metastatic breast cancer. Semin Oncol, 2002,29(3 Suppl 11): 38-43
[83] Coiffier B. Rituximab in combination with CHOP improves survival in elderly patients with aggressive non-Hodgkin's lymphoma. Semin Oncol, 2002, 29(2 Suppl 6): 18-22
[84] Francis RJ, Sharma SK, Springer C, Green AJ, Hope-Stone LD, Sena L, Martin J, Adamson KL, Robbins A, Gumbrell L, O'Malley D, Tsiompanou E, Shahbakhti H, Web-ley S, Hochhauser D, Hilson AJ, Blakey D, Begent RH. A phase I trial of antibody direc- ted enzyme prodrug therapy (ASEPT) in patients with colorectal carcinoma or other CEA producing tumours. Br J Cancer, 2002, 87(6): 600-607
[85] DeWeese TL, van der Poel H, Li S, Mikhak B, Drew R, Goemann M, Hamper U, DeJong R, Detorie N, Rodriguez R, Haulk T, DeMarzo AM, Piantadosi S, Yu DC, Chen Y, Henderson DR, Carducci MA, Nelson WG, Simons JW. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res, 2001, 61(20): 7464- 7472
[86] Whelan M, Whelan J, Russell N, Dalgleish A. Cancer immunotherapy: an embarrassment of riches? Drug Discov Today, 2003, 8(6): 253-258
[87] Baldwin RW. Immunity to methylcholanthrene-induced tumors in inbred rats following atrophy and implanted tumors. Br J Cancer, 1955,9: 652-665
[88] Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst, 1957,18:769-778
[89] Klein G, Sjogren HO, Klein E, Hellstrom KE. Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res, 1960,20: 1561-1572
[90] Boon T, Coulie PG, Van den Eynde B.Tumor antigens recognized by T cells. Immunol Today, 1997, 18(6): 267-268
[91] van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991, 254(5038): 1643-1647
[92] Stevanovic S. Identification of tumor-associated T-cell epitopes for vaccine development. Nature Rev, 2002, 2: 1-7
[93] Chen YT, Scanlan MJ, Sahin U. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA, 1997,94: 1914-1918
[94] Gabrilovich DI, Nadaf S, Corak J, Berzofsky JA, Carbone DP. Dendritic cells in an- titumor immune responses. II. Dentritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors. Cell Immunol, 1996, 170 (1): 111-119
[95] Herin M, Lemoine C, Weynants P, Vessiere F, Van Pel A, Knuth A, Devos R, Boon T. Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int. J. Cancer, 1987, 39: 390-396
[96] Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res, 2001, 61(14): 5544-5551
[97] Dabovic B, Zanaria E, Bardoni B, Lisa A, Bordignon C, Russo V, Matessi C, Traversari C, Camerino G. A family of rapidly evolving genes from the sex reversal critical region in Xp21. Mamm. Genome, 1995, 6(9): 571-580
[98] Muscatelli F, Walker AP, De Plaen E, Stafford AN, Monaco AP. Isolation and characterization of a new MAGE gene family in the Xp21.3 region. Proc Natl Acad Sci USA,1995, 92(11): 4987-4991
[99] Lucas S, De Smet C, Arden KC, Viars CS, Lethe B, Lurquin C, Boon T. Identifica tion of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res, 1998, 58(4): 743-752
[100] Lucas S, De Plaen E, Boon T. MAGE-B5, MAGE-B6, MAGE-C2 and MAGE-C3: four new members of the MAGE family with tumor-specific expression, Int J Cancer, 2000, 87:55-60
[101] Lucas S, Brasseur F, Boon T. A new MAGE gene with ubiquitous expression does not code for known MAGE antigens recognized by T cells. Cancer Res, 1999, 59: 4100-4103
[102] Pold M, Zhou J, Chen GL, Hall JM, Vescio RA, Berenson JR. Identification of a new, unorthodox member of the MAGE gene family. Genomics, 1999, 59(2): 161-167
[103] Lurquin C, De Smet C, Brasseur F, Muscatelli F, Martelange V, De Plaen E, Brasseur R, Monaco AP, Boon T. Two members of the human MAGEB gene family located in Xp21.3 are expressed in tumors of various histological origins. Genomics, 1997, 46(3): 397-408
[104] Kawano Y, Sasaki M, Nakahira K, Yoshimine T, Shimizu K, Wada H, Ikenaka K. Structural characterization and chromosomal localization of the MAGE-E1 gene. Gene, 2001, 277(1-2): 129-137
[105] Fukuda MN, Sato T, Nakayama J, Klier G, Mikami M, Aoki D, Nozawa S. Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation. Gene Dev., 1995, 9: 1199-1210
[106] Suzuki N, Nadano D, Paria BC, Kupriyanov S, Sugihara K, Fukuda MN. Trophinin expression in the mouse uterus coincides with implantation and is hormoneally regulated but not induced by implanting blastocysts. Endocrinology, 2000, 141: 4247-4254
[107] De Plaen E, De Backer O, Arnaud D, Bonjean B, Chomez P, Martelange V, Avner P, Baldacci P, Babinet C, Hwang SY, Knowles B, Boon T. A new family of mouse genes homologous to the human MAGE genes. Genomics, 1999, 55: 176-184
[108] De Backer O, Verheyden AM, Martin B, Godelaine D, De Plaen E, Brasseur R, Avner P, Boon T. Structural, chromosomal location, and expression pattern of three mouse homologous to the human MAGE genes. Genomics, 1995, 28(1): 47-83
[109] Eura M, Chikamatsu K, Ogi K, Nakano K, Masuyama K, Ishikawa T. Expression of genes MAGE-1, -2, and -3 by human maxillary carcinoma cells. Anticancer Res, 1995, 15(1): 55-59
[110] Eura M, Ogi K, Chikamatsu K, Lee KD, Nakano K, Masuyama K, Itoh K, Ishikawa T. Expression of the MAGE gene Family in human head-and-neck squamous cell carcinomas. Int J Cancer, 1995, 64(5): 304-308
[111] Quillien V, Raoul JL, Heresbach D, Collet B, Toujas L, Brasseur F. Expression of MAGE genes in esophageals squamous cell carcinoma. Anticancer Res, 1997, 17(1A): 387-391
[112] Li J, Yang Y, Fujie T, Tanaka F, Mimori K, Haraguchi M, Ueo H, Mori M, Akiyoshi T. Expression of the MAGE gene family in human gastric carcinoma. Anticancer Res, 1997, 17(5A): 3559-3563
[113] Yoshimatsu T, Yoshino I, Ohgami A, Takenoyama M, Hanagiri T, Nomoto K, Yasumoto K. Expression of the melanoma antigen encoding gene in human lung cancer. J Surg Oncol, 1998, 67(2): 126-129
[114] Hasegawa H, Mori M, Haraguchi M, Ueo H, Sugimachi K, Akiyoshi T. Expression spectrum of melanoma antigen encoding gene family members in colorectal carcinoma. Arch Pathol Lab Med, 1998, 122(6): 551-554
[115] Tahara K, Mori M, Sadanaga N, Sakamoto Y, Kitano S, Makuuchi M. Expression of the MAGE gene family in human hepatocellular carcinoma. Cancer, 1999, 85(6): 1234-1240
[116] Chen YT, Stockert E, Chen Y, Garin-Chesa P, Rettig WJ, van der Bruggen P, Boon T, Old LJ. Identification of the MAGE-1 gene product by monoclonal and polyclonal an- tibodies. Proc Natl Acad Sci USA, 1994, 91(3): 1004-1008
[117] Kocher T, Schultz-Thater E, Gudat F, Schaefer C, Casorati G, Juretic A, Willimann T, Harder F, Heberer M, Spagnoli GC. Identification and intracellular location of MAGE-3 gene product. Cancer Res, 1995, 55(11): 2236-2239
[118] Shichijo S, Hayashi A, Takamori S, Tsunosue R, Hoshino T, Sakata M, Kuramoto T, Oizumi K, Itoh K. Detection of MAGE-4 protein in lung cancers. Int J Cancer, 1995, 64(3): 158-165
[119] 蔡胜利,冷希圣,杜如昱.肿瘤特异性抗原-MAGE家族的研究进展.中华外科杂志,2001,39(8):645-647
[120] Sasaki M, Nakahira K, Kawano Y, Katakura H, Yoshimine T, Shimizu K, Kim SU, Ikenaka K. MAGE-E1, a new member of the melanoma-associated antigen gene family and its expression in human glioma. Cancer Res, 2001, 61: 4809-4814
[121] Janssen BL, van de Locht LT, Fourkour A, de Smet C, Mensink EJ, van Muijen GN, de Vries TJ. Transcription of the MAGE-1 gene and the methylation status of its Ets binding promoter elements: a quantitative analysis in melanoma cell lines using a real time polymerase chain reaction technique. Melanoma Res, 1999, 9(3): 213-22
[122] Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, Lassam N, Treisman J, Rosenberg SA. Expression of the MAGE-1 tumor antigen is upregulated by the demethylatingagent 5-aza-2'-deoxycytidine. Cancer Res, 1994, 54(7): 1766-1771
[123] Mori M, Inoue H, Mimori K, Shibuta K, Baba K, Nakashima H, Haraguchi M, Tsuji K, Ueo H, Barnard GF, Akiyoshi T. Expression of MAGE genes in human colorectal carcinoma. Ann Surg, 1996, 224(2): 183-188
[124] Shichijo S, Yamada A, Sagawa K, Iwamoto O, Sakata M, Nagai K, Itoh K. Induction of MAGE genes in lymphoid cells by the demethylatingagent 5-aza-2'-deoxycytidine. Jpn J Cancer Res, 1996, 87(7): 751-756
[125] De Smet C, Lurquin C, Lethe B, Martelange V, Boon T. DNA methylation is the primary silencing mechanism for a set of germline and tumor specific genes with a CpG rich promoter. Mol Cell Biol, 1999, 19(11): 7327-7335
[126] De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur R, Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc. Natl. Acad. Sci. USA, 1996, 93: 7149-7153
[127] Takahash K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 protein in spernatogonia and primary spermaticytes of testis. Cancer Res, 1995, 55: 3478-3482
[128] Osterlund C, Tohomem V, Forslund KO, Nordqvist K. Mage-b4, a novel melanoma antigen(MAGE) gene specifically expressed during germ cell differentiation. Cancer Res, 2000, 60: 1054-1061
[129] Taniura H, Taniguchi N, Hara M, Yoshikawa K. Necdin, a postmiotic neron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J Biol Chem, 1998, 273: 720-728
[130] Taniura H, Matsumoto K, Yoshikawa K. Physical and functionl interactions of neuronal growth suppressor necdin with p53. J Biol Chem, 1999, 274 (23): 16242-16248
[131] Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA. NRAGE, a novel MAGE protein, interacts with the p75 neuro-trophin receptor and facilitates nerve growthfactor-dependent apoptosis. Neuron, 2000, 27(2): 279-288
[132] Jordan BW, Dinev D, Le Mellay V, Troppmair J, Gotz R, Wixler, Sendtner M, Ludwig S, Rapp UR. Neurotrophin receptor-interacting Mage homoiogue is an inducible inhibitor of apoptosis protein-interacting protein thet augments cell death. J. Biol. Chem, 2001, 276(43): 39985-39989
[133] Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev, 2002, 188(1): 22-32
[134] Panelli MC, Bettinotti MP, Lally K, Ohnmacht GA, Li Y, Robbins P, Riker A, Rosenberg SA, Marincola FM. A tumor-infiltrating lymphocyte from a melanoma metastasis with decreased expression of melanoma differentiation an-tigens recognizes MAGE-12. J Immunol, 2000, 164(8): 4382-4390
[135] Gajewski TF, Fallarino F, Ashikari A, Sherman M. Immunization of HLA-A2+ melanoma patients with MAGE-3 or MelanA peptide-pulsed autologous peripheral blood mononuclear cells plus recombinant human interleukin 12. Clin Cancer Res, 2001, 7(3 Suppl): 895-901
[136] Serrano A, Lethe B, Delroisse JM, Lurquin C, De Plaen E, Brasseur F, Rimoldi D, Boon T. Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries. Int J Cancer, 1999, 83(5): 664-649
[137] Hillig RC, Coulie PG, Stroobant V, Saenger W, Ziegler A, Hulsmeyer M. High-resolution structure of HLA-A~*0201 in complex with a tumour-specific antigenic peptide encoded by the MAGE-A4 gene. J Mol Biol, 2001, 310(5): 1167-1176
[138] Heidecker L, Brasseur F, Probst-Kepper M, Gueguen M, Boon T, Van den Eynde BJ. Cytolytic T lymphocytes raised against a human bladder carcinoma recognize an antigen encoded by gene MAGE-A 12. J Immunol, 2000, 164(11): 6041-6045
[139] Jaeger E, Bernhard H, Romero P, Ringhoffer M, Arand M, Karbach J, Ilsemann C, Hagedorn M, Knuth A. Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Int J Cancer, 1996, 66(2): 162-169
[140] Graff-Dubois S, Faure O, Gross DA, Alves P, Scardino A, Chouaib S, Lemonnier FA, Kosmatopoulos K. Generation of CTL recognizing an HLA-A~*0201-restricted epitope shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 tumor antigens: implication in a broad-spectrum tumor immunotherapy. J Immunol, 2002, 169(1): 575-580
[141] Marchand M, Punt CJ, Aamdal S, Escudier B, Kruit WH, Keilhoiz U, Hakansson L, van Baren N, Humblet Y, Mulders P, Avril MF, Eggermont AM, Scheibenbogen C, Uiters J, Wanders J, Delire M, Boon T, Stoter G. Immunization of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur J Cancer, 2003, 39(1): 70-77
[142] Hoon DS, Yuzuki D, Hayashida M, Morton DL. Melanoma patients immunized with melanoma cell vaccine induce antibody responses to recombinant MAGE-1 antigen. J Immunol, 1995, 154(2): 730-737
[143] Reynolds SR, Oratz R, Shapiro RL, Hao P, Yun Z, Fotino M, Vukmanovic S, Bystryn JC. Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine. Int J Cancer, 1997, 72(6): 972-976
[144] Tjandrawan T, Martin DM, Maeurer MJ, Castelli C, Lotze MT, Storkus WJ. Autologous human dendriphages pulsed with synthetic or natural tumor peptides elicit tumor specific CTLs in vitro. J Immunother, 1998, 21(2): 149-157
[145] Sadanaga N, Nagashima H, Mashino K, Tahara K, Yamaguchi H, Ohta M, Fujie T, Tanaka F, Inoue H, Takesako K, Akiyoshi T, Mori M. Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res, 2001, 7(8): 2277-2784
[146] Berard F, Blanco P, Davoust J, Neidhart-Berard EM, Nouri-Shirazi M, Taquet N, Rimoldi D, Cerottini JC, Banchereau J, Palucka AK. Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells. J Exp Med, 2000, 192(11): 1535-1544
[147] Tuting T, Wilson CC, Martin DM, Kasamon YL, Rowles J, Ma DI, Slingluff CL Jr, Wagner SN, van der Bruggen P, Baar J, Lotze MT, Storkus WJ. Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha. J Immunol, 1998, 160(3): 1139-1147
[148] Bueler H, Mulligan RC, Induction of antigen specific tumor immunity by genetic and cellular vaccines against MAGE: enhanced tumor protection by coexpression of granulocyte macrophagecolony stimulating factor and B7.1. Mol Med, 1996, 2(5): 545-555
[149] Sun X, Hodge LM, Jones HP, Tabor L, Simecka JW. Co-expression of granulocyte-macrophage colony-stimulating factor with antigen enhances humoral and tumor immunity after DNA vaccination. Vaccine, 2002, 20(9-10): 1466-1474
[150] Hoon DS, Wang Y, Dale PS, Conrad AJ, Schmid P, Garrison D, Kuo C, Foshag LJ, Nizze A J, Morton DL. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol, 1995, 13(8): 2109-2016
[151] Iwamoto O, Nagao Y, Shichijo S, Eura M, Kameyama T, Itoh K. Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell carcinoma. Int J Cancer, 1997, 70(3): 287-290
[152] Liu BB, Ye SL, He P, Liu YK, Tang ZY. MAGE-1 and related MAGE gene expression may be associated with hepatocellular carcinoma. J Cancer Res Clin Oncol, 1999, 125(12): 685-689
[153] 蔡胜利,陈红松,王瑜,赵海涛,彭吉润,庞学文,龚顺友,朱继业,丛旭,王宇,芮静安,冷圣希,杜如昱,陈慰峰.黑色素瘤抗原-1基因在肝细胞癌中的表达.中华医学杂志,1999,79:668-671
[154] 武文,隋延仿,叶菁,等.人肝癌细胞系中肿瘤相关基因MAGE的克隆.细胞与分子免疫学杂志,2002,18:270-274
[155] 董海龙,随延仿,叶菁,李增山,曲萍,张秀敏,陈广生,禄韶英.肿瘤抗原MAGE-n HLA-A2限制性细胞毒性T细胞表位的预测及合成鉴定.中华医学杂志,2003,83(11):1-4
[156] Hailong Dong, Yanfang Sui, Zengshan Li, Ping Qu, Wen Wu, Jing Ye, Xiumin Zhang, Shaoying Lu. Efficient induction of cytotoxic T lymphocytes specific to heaptocellular carcinoma using HLA-A2-restricted MAGE-n peptide in vitro. Cancer Letter, 2004, 211: 219-225
[157] Tighe H, Corr M, Roman M, Raz E. Gene vaccination: plasmid DNA is more than just a bluerint. Immunol Today, 1998, 19(2): 89-97
[158] Levitsky HI. Accessories for naked DNA vaccines. Nat Biotechnol, 1997, 15(7): 619-620
[159] Reimann J, Kaufmann SH. Alternative antigen processing pathways in anti-infective immunity. Curr Opin Immunol, 1997, 9(4): 462-469
[160] Stenger S, Modlin RL. Cytoxic T cell responses to intracellular pathogens. Curr Opin Immunol, 1998, 10(4): 471-477
[161] Reise Sousa C, Sher A, Kaye P. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Ocrr Opin Immunol, 1999, 11(4): 392-399
[162] Gustafsson J, Arvidson G, Karlsson G, Almgren M. Complexes between cationic liposomes and DNA visualized by cryo-TEM. Biochim Biophys Acta, 1995, 1235(2): 305-312
[163] Farthood H, Serbina N, Huang L. The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. Biochim Biophys Acta, 1995, 1235(2): 289
[164] Pinnaduwage P, Schmitt L, Huang L. Use of a quaternary ammonium detergent in liposome mediated DNA transfection of mouse L cells. Biochim Biophys Acta, 1989, 985(1): 33
[165] Gao X, Huang L. A novel cationic liposome reagent for efficient transfection in mammalian cells. Biochem Biophys Res Commun,1991, 179(1): 280
[166] Felgner PL, Ringold GM. Cationic liposomes-mediated transfection. Nature, 1989, 337(6205): 387
[167] Radler JO, Koltover I, Salditt T, Safinya CR. Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science, 1997, 275(5301): 810-814
[168] Nily D. Multilamellar structures of DNA complexes with cationic liposomes. Biophys J, 1997, 73(4): 1842-1846
[169] Spector MS, Schnur JM. DNA ordering on a lipid membrane. Science, 1997, 275 (5301): 791-792
[170] Farhood H, Gao X, Barsoum J, Huang L. Codelivery mammalian cells of a transcriptional factor with cis-acting element using cationic liposomes. Anal Biochem, 1995, 225(1): 89-93
[171] Hofland H, Huang L, Inhibition of human ovarian carcinoma cell proliferation by liposome-plasmid DNA complex. Biochem Biophys Res Commun, 1995, 207(2): 492
[172] 卢大儒,邱信芳,薛京伦.基因治疗转移方法的研究进展.国外医学·遗传学分册,1996,19(1):1
[173] Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE. Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity and lack of toxicity in human. Proc Natl Acad Sci USA, 1993, 90(23): 11307-11311
[174] 王军志,丁锡申.国外基因治疗临床研究动向及市场展望.生物工程进展,1997,17(3):56
[175] Yoshida J, Mizuno M. Simple method to prepare cationic multilamellar liposomes for efficient transfection of human interferon-beta gene to human glioma cells. J Neurooncal, 1994, 19(3): 269
[176] 陈敏亮,林子豪,曹雪涛,王全兴,于益之,朱晓海,赵耀中,刘麒,袁相斌.鳞癌瘤体内注射脂质体包裹的人α干扰素基因的抗肿瘤治疗.第二军医大学学报,2000,21(11):1068-1070
[177] 王克敏,赵宇,张景迎,夏爱娣,陈诗书.阳离子脂质体介导细胞因子基因对小鼠肝癌抑制的作用.上海第二医科大学学报,1999,6(19):504-507
[178] Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature, 1995, 374(6522): 546-549
[179] Krieg AM, Roman M. Mechanisms and applications of immunostimulatory CpG oligodeoxynucleotides. Biochimica et Biophysica Acta, 1999, 1949:107
[180] Lipford GB, Bauer M, Blank C, Reiter R, Wagner H, Heeg K. CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen. Eur J Immunol, 1997, 27(9): 2340-2344
[181] Yi AK, Hornbeck P, Lafrenz DE, Krieg AM. CpG DNA rescue of murine B lym- phoma cells from anti-IgM-induced growth arrest and programmed cell death is associated with increased expression of c-myc and bcl-xL. J Immunol, 1996, 157(11): 4918- 4925
[182] Yi AK, Krieg AM. CpG DNA rescue from anti-IgM-induced WEIHI-231 B lympho-ma apoptosis via modulation of I kappa B alpha and I kappa N beta and sustained activation of nuclear factor-kappa B/c-Rel. J Immunol, 1998, 160 (3): 1240-1245
[183] Sparwasser T, Koch ES, Vabulas RM, Heeg K, Lipford GB, Ellwart JW, Wagner H. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol, 1998,28(6): 2045-2054
[184] Ballas ZK, Rasmussen WL, Krieg AM. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J Immunol, 1996, 157(5): 1840-1845
[185] Chace JH, Hooker NA, Mildenstein KL, Krieg AM, Cowdery JS. Bacterial DNA-nduced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12. Clin Immunol Immunopathol, 1997, 84(2): 185-193
[186] Halpern MD, Kurlander RJ, Pisetsky DS. Bacterial DNA induces murine interferon-gamma production by stimulation of interleukin-12 and tumor necrosis factor-alpha. Cell Immunol, 1996, 167(1): 72-78
[187] Bendigs S, Salzer U, Lipford GB, Wagner H, Heeg K. CpG-oligodeoxynucleotides costimulate primary T cells in the absence of antigen presenting cells. Eur J Immunol, 1999,29(4): 1209-1218
[188] Oxenius A, Martinic MM, Hengartner H, Klenerman P. CpG-containing oligonucleotides are efficient adjuvants for induction of protective antiviral immune responses with T cell peptide vaccines. J Virol, 1999, 73(5): 4120-4126
[189] Yi AK, Krieg AM. Rapid induction of Mitogen-activated protein kinases by immune stimulatory CpG DNA. J Immunol, 1998, 161:4493
[190] Yi AK, Tuetken R, Redford T, Waldschmidt M, Kirsch J, Krieg AM. CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. J Immunol, 1998, 160(10): 4755-61
[191] Hacker H. Signal transduction pathways activated by CpG-DNA. Curr Top Mcro-biol Immunol, 2000, 247: 77
[192]Macfarlane DE, Manzel L. Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds. J Immonol,1998, 160(3): 1122-1131
[193] Weiner GJ, Liu HM, Wooldridge JE, Dahle CE, Krieg AM. Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization. Proc Natl Acad Sci USA, 1997, 94(20): 10833-10837
[194] Wooldridge JE, Ballas Z, Krieg AM, Weiner GJ. Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma. Blood, 1997, 89(8): 2994-2998
[195] Schlossman SF, Boumsell L, Gilks W, Harlan JM, Kishimoto T, Morimoto C, Ritz J, Shaw S, Silverstein RL, Springer TA. CD antigens 1993. Immu- nol Today, 1994, 15(3): 98-99
[196] Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, Banche-reau J. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med, 1994, 180(5): 1841-1847
[197] Boussiotis VA, Freeman GJ, Gribben JG, Nadler LM. The role of B7-1/ B7-2: CD28/CLTA-4 pathways in the prevention of anergy, induction of productive immunity and down-regulation of the immune response. Immunol Rev, 1996, 153: 5-26
[198] Thurnher M, Radmayr C, Hobisch A, Bock G, Romani N, Bartsch G, Klocker H. Tumor-infiltrating T lymphocytes from renal-cell carcinoma express B7-1 (CD80): T-cell expansion by T-T cell co-stimulation. Int J Cancer, 1995,62(5): 559-564
[199] Pichler WJ, Tony Wyss Coray. T cells as antigen-presenting cells. Immunol Today, 1994,15(7): 312-315
[200] Denfeld RW, Dietrich A, Wuttig C, Tanczos E, Weiss JM, Vanscheidt W, Schopf E, Simon JC. In situ expression of B7 and CD28 receptor families in hu- man malignant melanoma: relevance for T-cell-mediated anti-tumor immunity. Int J Cancer, 1995,62(3): 259-265
[201] Chen L, Ashe S, Brady WA, Hellstrom I, Hellstrom KE, Ledbetter JA, McGowan P, Linsley PS. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell, 1992, 71 (7): 1093-1102
[202] Mochizuki K, Hayashi N, Katayama K, Hiramatsu N, Kanto T, Mita E, Tatsumi T, Kuzushita N, Kasahara A, Fusamoto H, Yokochi T, Kamada T. B7/ BB-1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C. Hepatology, 1997, 25 (3): 713-718
[203] Tatsumi T, Takehara T, Katayama K, Mochizuki K, Yamamoto M, Kanto T, Sasaki Y, Kasahara A, Hayashi N. Expression of costimulatory molecules B7-1 (CD80) and B7- 2 (CD86) on human hepatocellular carcinoma. Hepatology, 1997, 25(5): 1108-1114
[204] Pettit SJ, Ali S, O'Flaherty E, Griffiths TR, Neal DE, Kirby JA. Bladder cancer im- munogenicity: expression of CD80 and CD86 is insufficient to allow primary CD4+ T cell activation in vitro. Clin Exp Immunol, 1999,116(1): 48-56
[205] Hideki F, Manabu I, Fuminari K, Jun M, Masaaki M, Yasuharn O, Ichiro A, Toshi- mitsu U Ikuo S. Vaccination of tumor transfected with the B7-l(CD80) Gene induces the anti-metastatic effect and tumor immunity in mice. Int J Cancer, 1996, 66: 219-224
[206] Gaken JA, Hollingsworth SJ, Hirst WJ, Buggins AG, Galea-Lauri J, Peakman M, Kuiper M, Patel P, Towner P, Patel4 PM, Collins MK, Mufti GJ, Farzaneh F, Darling DC. Irradiated NC adenocarcinoma cells transduced with both B7.1 and interleukin-2 induce CD4+-mediated rejection of established tumors. Hum Gene Ther, 1997, 8(4): 477-488
[207] Kato K, Okumura K, Yagita H. Immunoregulation by B7 and IL-12 gene transfer. Leukemia, 1997, 11(Suppl 3): 572-576
[208] Putzer BM, Hitt M, Muller WJ, Emtage P, Gauldie J, Graham FL. Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression. Proc Natl Acad Sci USA, 1997, 94 (20): 10889-10894
[209] Cayeux S, Beck C, Dorken B, Blankenstein T. Coexpression of interleukin-4 and B7.1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant. Hum Gene Ther, 1996, 7(4): 525-529
[210] Parney IF, Petruk KC, Zhang C, Farr-Jones M, Sykes DB, Chang LJ. Granulocyte- macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model. Hum Gene Ther, 1997; 8(9):1073-1085
[201] Yang S, Vervaert CE, Seigler HF, Darrow TL. Tumor cells cotransduced with B7.1 and gamma-IFN induce effective rejection of established parental tumor. Gene Ther, 1999; 6(2): 253-262
[212] Pulaski BA, Ostrand-Rosenberg S. Reduction of established spontaneous mammary carcinoma metastases following immunotherapy with major histocompatibility complex class Ⅱ and B7.1 cell-based tumor vaccines. Cancer Res, 1998, 58(7): 1486-1493
[213] Zajac P, Schutz A, Oertli D, Noppen C, Schaefer C, Heberer M, Spagnoli GC, Marti WR. Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules. Cancer Res, 1998; 58(20): 4567-4571
[214] Imro MA, Dellabona P, Manici S, Heltai S, Consogno G, Bellone M, Rugarli C, Protti MP. Human melanoma cells transfected with the B7-2 co-stimulatory molecule induce tumor-specific CD8+ cytotoxic T lymphocytes in vitro. Hum Gene Ther, 1998, 9(9): 1335-1344
[215] Cayeux S, Richter G, Becker C, Beck C, Aicher A, Pezzutto A, Dorken B, Blankenstein T. Lack of correlation between rejection of tumor cells co-expressing interleukin-2 and B7.1 and vaccine efficiency. Eur J Immunol, 1997, 27(7): 1657-1662
[216] Musgrave BL, Phu T, Butler JJ, Makrigiannis AP, Hoskin DW. Murine TRAIL (TNF-related apoptosis inducing ligand) expression induced by T cell activation is blocked by Rapamycin, cyclosporin A, and inhibitors of phosphatidylinositol 3-kinase, protein kinase C, and protein tyrosine kinase: evidence for TRAIL induction via the T cell receptor signaling pathway. Exp Cell Res, 1999, 252(1): 96-103
[217] 李春英,高天文.恶性黑素瘤核酸疫苗免疫影响因素及对策.国外医学皮肤性病学分册,2001,27(5):288-290
[218] Itoh K, Hayashi A, Nakao M, Hoshino T, Seki N, Shichijo S. Human tumor rejecttion antigens MAGE. J Biochem Tokyo, 1996, 119(3): 385-390
[219] Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, Kurtzman SK, Ergin MT, Ozols J, Meehan J. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci U S A, 1995, 92 (17): 8078-8082
[220] Lu J, Leng X, Peng J, Mou D, Pang X, Shang X, Chen W. Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide. Chin Med J (Engl), 2002, 115(7): 1002-1005
[221] Ye J, Chen GS, Song HP, Li ZS, Huang YY, Qu P, Sun YJ, Zhang XM, Sui YF. Heatshock protein 70/MAGE-1 tumor vaccine can enhance the potency of MAGE-1-specific cellular immune responses in vivo. Cancer Immunol Immuno Ther, 2004, 53(9): 825-834
[222] Ma JH, Sui YF, Ye J, Huang YY, Li ZS, Chen GS, Qu P, Song HP, Zhang XM. Heat shock protein 70/MAGE-3 fusion protein vaccine can enhance cellular and humoral im mune responses to MAGE-3 in vivo. Cancer Immunol Immunother, 2005, Mar 9, in pub lication
[223] Hurwitz AA, Townsend SE, Yu TF, Wallin JA, Allison JP. Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma. Int J Cancer, 1998, 77(1): 107-113
[224] Vasilevko V, Ghochikyan A, Sadzikava N, Petrushina I, Tran M, Cohen EP, Kesslak PJ, Cribbs DH, Nicolson GL, Agadjanyan MG. Immunization with a vaccine that combines the expression of MUC 1 and B7 co-stimulatory molecules prolongs the survival of mice and delays the appearance of mouse mammary tumors. Clin Exp Metastasis, 2003, 20(6): 489-98
[225] Disis ML, Scholler N, Dahlin A, Pullman J, Knutson KL, Hellstrom KE, Hellstrom I. Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity. Mol Cancer Ther, 2003, 2(10): 995-1002
[2] Gillespie AM, Coleman RE. The potential of melanoma antigen expression in cancer therapy. Cancer Treat Rev, 1999, 25(4): 219-227
[3] 龙振洲.医学免疫学.第二版.北京:人民卫生出版社,1996,136
[4] Schlom J, Hodge JW. The diversity of T-cell co-stimulation in the induction of antitumor immunity. Immunol Rev, 1999, 170:73-84
[5] 金伯泉.细胞和分子免疫学.第二版.北京:科学出版社,2001,417-418
[6] Schuurhuis DH, Ioan-Facsinay A, Nagelkerken B, van Schip JJ, Sedlik C, Melief CJ, Verbeek JS, Ossendorp F. Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CDS+ CTL responses in vivo. J Immunol, 2002, 168(5): 2240-2246
[7] Belz GT, Carbone FR, Heath WR. Cross-presentation of antigens by dendritic cells. Crit Rev Immunol, 2002, 22(5-6): 439-448
[8] Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H. The central role of CD4(+) T cells in the antitumor immune response. J Exp Med, 1998, 188(12): 2357-2368
[9] Zeng G, Wang X, Robbins PF, Rosenberg SA, Wang RF. CD4(+) T cell recognition of MHC class Ⅱ-restricted epitopes from NY-ESO-1 presented by a prevalent HLA DP4 allele: association with NY-ESO-1 antibody production. Proc Natl Acad Sci USA, 2001, 98(7): 3964-3969
[10] Adris S, Chuluyan E, Bravo A, Berenstein M, Klein S, Jasnis M, Carbone C, Chernajovsky Y, Podhajcer OL. Mice vaccination with interleukin 12-transduced colon cancer cells potentiates rejection of syngeneic non-organ-related tumor cells. Cancer Res, 2000, 60(23): 6696-6703
[11] 宫恩聪,丁彦青,黄高昇.大学病理学.北京:高等教育出版社,2001,130
[12] Boon T, van Baren N. Immunosurveillance against cancer and immunotherapy-synergy or antagonism? N Engl J Med, 2003, 348(3): 252-254
[13] Ochsenbein AF. Principles of tumor immunosurveillance and implications for immunotherapy. Cancer Gene Ther, 2002, 9(12): 1043-1055
[14] Gatti RA, Good TA. Occurrence of malignancy in immunodeficiency diseases. A literature review. Cancer, 1971, 28(1): 89-98
[15] Halliday GM, Le S. Transforming growth factor-beta produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin. Int Immunol, 2001, 13(9): 1147-1154
[16] Riker A, Cormier J, Panelli M, Kammula U, Wang E, Abati A, Fetsch P, Lee KH, Steinberg S, Rosenberg S, Marincola F. Immune selection after antigen-specific immunotherapy of melanoma. Surgery, 1999, 126(2): 112-120
[17] Garrido F, Ruiz-Cabello F, Cabrera T, Perez-Villar JJ, Lopez-Botet M, Duggan-Keen M, Stern PL. Implications for immunosurveillance of altered HLA class Ⅰ phenotypes in human tumours. Immunol Today, 1997, 18(2): 89-95
[18] Youngchun B, Jianqiong Z, Zehui H. Association of HLA class Ⅰ antigen expression in human hepatocellar carcinoma with improved prognosis. Tissue Antigens, 2002, 59 (Suppl 2): 105-106
[19] Real LM, Jimenez P, Canton J, Kirkin A, Garcia A, Abril E, Zeuthen J, Ruiz-Cabello F, Garrido F. In vivo and in vitro generation of a new altered HLA phenotype in melanoma-tumour-cell variants expressing a single HLA-class-I allele. Int J Cancer, 1998, 75(2): 317-323
[20] Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Scienc, 1990, 248(4961): 1349-1356
[21] Li W, Rosenzweig A, Huber BT. Differential T-cell activation by B7-1 expression. Immunology, 2003, 109(3): 336-342
[22] Rogers NJ, Jackson IM, Jordan WJ, Hawadle MA, Dorling A, Lechler RI. Cross-species costimulation: relative contributions of CD80, CD86, and CD40. Transplantation,2003, 75(12): 2068-2076
[23] Salazar-Onfray F. Interleukin-10: a cytokine used by tumors to escape immunosur-veillance. Med Oncol, 1999, 16(2): 86-94
[24] Ke Y, Kapp LM, Kapp JA. Inhibition of tumor rejection by gammadelta T cells and IL-10. Cell Immunol, 2003,221(2): 107-114
[25] Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, Akdis CA. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol, 2003, 33(5): 1205-1214
[26] Chen W, Frank ME, Jin W, Wahl SM. TGF-P released by apoptotic T cells contributes to an immunosuppressive milieu. Immunity, 2001, 14(6): 715-725
[27] Ebert EC. Inhibitory effects of transforming growth factor-beta (TGF-beta) on certain functions of intraepithelial lymphocytes. Clin Exp Immunol, 1999, 115(3): 415-420
[28] Ristimaki A, Honkanen N, Jankala H, et al. Expression of cycleocoxygenase 2 in human gastric carcinoma. Cancer Res, 1997, 57(7): 1276-1280
[29] Eisengart CA, Mestre JR, Naama HA, Mackrell PJ, Rivadeneira DE, Murphy EM, Stapleton PP, Daly JM. Prostaglandins regulate melanoma-induced cytokine production in macrophages. Cell Immunol, 2000,204(2): 143-149
[30] Toi M, Taniguchi T, Yamamoto Y, Kurisaki T, Suzuki H, Tominaga T. Clinical significance of the determination of angiogenic factors. Eur J Cancer, 1996, 32A(14): 25 13-2539
[31] Oyama T, Ran S, Ishida T, Nadaf S, Kerr L, Carbone DP, Gabrilovich DI. Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. J Immunol, 1998, 160(3): 1224-1232
[32] Saito H, Tsujitani S, Ikeguchi M, Maeta M, Kaibara N. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer, 1998, 78(12): 1573-1577
[33] Voorzanger N, Touitou R, Garcia E, Delecluse HJ, Rousset F, Joab I, Favrot MC, Blay JY. Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin's lymphoma cells and act as cooperative growth factors. Cancer Res, 1996, 56(23): 5499-5505
[34] Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Pal-ucka K. Immunobiology of dendritic Cells. Annu Rev Immunol, 2000, 18: 767-811
[35] Carbone JE, Ohm DP. Immune dysfunction in cancer patients. Oncology (Huntingt),2002, 16(1 Suppl 1): 11-18
[36] Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kava-naugh D, Carbone DP. Production of vascular endothelial growth factor by tumors inhi- bits the functional maturation of dendritic cells. Nat Med, 1996, 2(10): 1096-1103
[37] Lespagnard L, Gancberg D, Rouas G, Leclercq G, de Saint-Aubain Somerhausen N, Di Leo A, Piccart M, Verhest A, Larsimont D. Tumor-infiltrating dendritic cells in adenocarcinomas of the breast: a study of 143 neoplasms with a correlation to usual prognostic factors and to clinical outcome. Int J Cancer, 1999, 84(3): 309-314
[38] Chaux P, Favre N, Martin M, Martin F. Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression in rats. Int J Cancer, 1997, 72(4): 619-624
[39] Zhu Q, Deng CS. Apoptosis of lymphocytes induced by Fas/FasL of colon cancer cells. Ai Zheng, 2002, 21(3): 272-275
[40] Rabinowich H, Reichert TE, Kashii Y, Gastman BR, Bell MC, Whiteside TL. Lymphocyte apoptosis induced by Fas ligand-expressing ovarian carcinoma cells. Implications for altered expression of T cell receptor in tumor-associated lymphocytes. J Clin Invest, 1998, 101(11): 2579-2588
[41] Cappello P, Novelli F, Forni G, Giovarelli M. Death receptor ligands in tumors. J Immunother, 2002, 25(1): 1-15
[42] Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Kayagaki N, Yagita H, Okumura K. Critical role for tumor necrosis factor-related apoptosis-induced ligand in immune surveillance against tumor development. J Exp Med, 2002, 195(2): 161-169
[43] Sakaguchi S, Sakaguchi N, Shimizu J, Yamazaki S, Sakihama T, Itoh M, Kuniyasu Y, Nomura T, Toda M, Takahashi T. Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev, 2001, 8(182): 18-32
[44] Wiemann B, Statues CO. Coley's toxins, tumor necrosis factor and cancer research: a historical perspective. Pharmacol Ther, 1994, 64(3): 529-564
[45] Hanna MG Jr, Hoover HC Jr, Vermorken JB, Harris JE, Pinedo HM. Adjuvant active specific immunotherapy of stage Ⅱ and stage Ⅲ trials colon cancer with an autologous tumor cell vaccine: first randomized phase Ⅱ trials show promise. Vaccine, 2001, 19 (17-19): 2576-2582
[46] Morton DL, Foshag LJ, Hoon DS, Nizze JA, Famatiga E, Wanek LA, Chang C, Davtyan DG, Gupta RK, Elashoff R, et al. Prolongation of survival in metastatic melanoma after active specific immunotherapy with a new polyvalent melanoma vaccine. Ann Surg, 1992, 216 (4): 463-482
[47] Thomas MC, Greten TF, Pardoll DM, Jaffee EM. Enhanced tumor protection by granulocyte-macrophage colony-stimulating factor expression at the site of an allogeneic vaccine. Hum Gene Ther, 1998, 9(6): 835-843
[48] Yang S, Darrow TL, Seigler HF. Generation of primary tumor-specific cytotoxic T lymphocytes from autoiogous and human lymphocyte antigen class Ⅰ-matched allogeneic peripheral blood lymphocytes by B7 gene-modified melanoma cells. Cancer Res, 1997, 57(8): 1561-1568
[49] Mullen CA, Petropoulos D, Lowe RM. Treatment of microscopic pulmonary metastases with recombinant autologous tumor vaccine expressing interleukin 6 and Escherichia coli cytosine deaminase suicide genes. Cancer Res, 1996, 56 (16): 1361-1366
[50] Willimsky G, Blankenstein T. Interleukin-7/B7.1-encoding adenoviruses induce rejection of transplanted but not nontransplanted tumors. Cancer Res, 2000, 60: 685
[51] 魏于全.抗肿瘤自身免疫反应与异种细胞疫苗研究进展.郭亚军主编.细胞生物学与肿瘤免疫学.北京:军事医学科学出版社,2000,208-218
[52] Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature, 1998 Mar 19, 392(6673): 245-252
[53] Nestle FO, Banchereau J, Hart D. Dendritic cells: On the move from bench to bedside. Nat Med, 2001, 7(7): 761-765
[54] Guo Y, Wu M, Chen H, Wang X, Liu G, Li G, Ma J, Sy MS. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science, 1994,263 (5146):518-520
[55] Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med, 1998,4(3): 328-332
[56] Brossart P, Wirths S, Stuhler G, Reichardt VL, Kanz L, Brugger W. Induction of cy-totoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood, 2000, 96(9): 3102-3108
[57] Nikitina EY, Chada S, Muro-Cacho C, Fang B, Zhang R, Roth JA, Gabrilovich DI. An effective immunization and cancer treatment with activated dendritic cells transduced with full-length wild-type p53. Gene Ther, 2002, 9 (5): 345-352
[58] Specht JM, Wang G, Do MT, Lam JS, Royal RE, Reeves ME, Rosenberg SA, Hwu P. Dendritic cells retrovirally transduced with a model antigen gene are therapeutically effective against established pulmonary metastases. J Exp Med, 1997, 186(8): 1213-1221
[59] Song W, Kong HL, Carpenter H, Torii H, Granstein R, Rafii S, Moore MA, Crystal RG. Dendritic cells genetically modified with a adenovirus vector encoding the cDNA for a model antigen induce protective and therapeutic antitumor immunity. J Exp Med, 1997, 186(8): 1247-1256
[60] Xia DJ, Zhang WP, Zheng S, Wang J, Pan JP, Wang Q, Zhang LH, Hamada H, Cao X. Lymphotactin cotransfection enhances the therapeutic efficacy of dendritic cells genetically modified with melanoma antigen gpl00. Gene Ther, 2002, 9(9): 592-601
[61] Kugler A, Stuhler G, Walden P, Zoller G, Zobywalski A, Brossart P, Trefzer U, Ullrich S, Muller CA, Becker V, Gross AJ, Hemmerlein B, Kanz L, Muller GA, Ringert RH. Regression of human metastatic renal cell carcinoma after vaccination with tumor celldendritic cell hybrids. Nat Med, 2000, 6(3): 332-336
[62] Wang J, Saffold S, Cao X, Krauss J, Chen W. Eliciting T cell immunity against poorly immunogenic tumor by immunization with dendritic cell-tumor fusion vaccines. J Im munol, 1998, 161(10): 5516-5524
[63] Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nature Med, 1997, 3(5): 558-561
[64] Lindner M, Schirrmacher V. Tumor cell-dendritic cell fusion for cancer immunothe-rapy: comparision of therpeutic efficiency of polyethylen-glycol versus electro-fusion protocols. Eur J Clin Invest, 2002, 32: 207-217
[65] Celluzzi CM, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD Jr. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity. J Exp Med, 1996, 183(1): 283-287
[66] Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Feigner PL. Direct gene transfer into mouse muscle in vivo. Science, 1990, 247(4949 Pt 1): 1465-1468
[67] Park JH, Kim CJ, Lee JH, Shin SH, Chung GH, Jang YS. Effective immunotherapy of cancer by DNA vaccination. Mol Cella, 1999, 9(4): 384-391
[68] Guo C, Ding J, Yu Z, Han Q, Meng F, Liu N, Fan D. Development of oral DNA vaccine based on MG(7)-Ag mimotope of gastric cancer. Zhonghua Zhong Liu Za Zhi, 2002,24(2): 110-113
[69] Walsh P, Gonzalez R, Dow S, Elmslie R, Potter T, Glode LM, Baron AE, Balmer C, Easterday K, Allen J, Rosse P. A phase I study using direct combination DNA injections for the immunotherapy of metastatic melanoma. Trial. Hum Gene Ther, 2000, 11 (9): 1355-1368
[70] Mincheff M, Tchakarov S, Zoubak S, Loukinov D, Botev C, Altankova I, Georgiev G, Petrov S, Meryman HT. Naked DNA and adenoviral immunizations for immunotherapy of prostate cancer: a phase I/II clinical trial. Eur Urol, 2000, 38 (2): 208-217
[71] Haupt K, Roggendorf M, Mann K. The potential of DNA vaccination against tumor-associated antigens for antitumor therapy. Exp Biol Med, 2002, 227 (4): 227-237
[72] Marshall JL, Hoyer RJ, Toomey MA, Faraguna K, Chang P, Richmond E, Pedicano JE, Gehan E, Peck RA, Arlen P, Tsang KY, Schlom J. Phase I study in advanced cancer patients of a diversified prime-and-boost vaccination protocol using recombinant vaccinia virus and recombinant nonreplicating avipox virus to elicit anti-carcinoembryonic antigen immune responses. J Clin Oncol, 2000, 18(23): 3964-3973
[73] Perambakam S, Xue BH, Sosman JA, Peace DJ. Induction of Tc2 cells with specificity for prostate-specific antigen from patients with hormone-refractory prostate cancer. Cancer Immunol Immunother, 2002, 51(5): 263-270
[74] Marchand M, van Baren N, Weynants P, Brichard V, Dreno B, Tessier MH, Rankin E, Parmiani G, Arienti F, Humblet Y, Bourlond A, Vanwijck R, Lienard D, Beauduin M, Dietrich PY, Russo V, Kerger J, Masucci G, Jager E, De Greve J, Atzpodien J, Brasseur F, Coulie PG, van der Bruggen P, Boon T. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE 3 and pre sented by HLA Al.Int J Cancer, 1999, 80(2): 219-230
[75] Jager E, Jager D , Knuth A . CTL-defined cancer vaccines: Perspectives for active immunotherapeutic interventions in minimal resdiual disease. Cancer and Metast Rev, 1999, 18:143-150
[76] Kim DK, Kim JH, Kim YT, Kim JW, Ioannides CG.The comparison of cytotoxic T- lymphocyte effects of dendritic cells stimulated by the folate binding protein peptide cultured with IL-15 and IL-2 in solid tumor. Yonsei Med J, 2002,43(6): 691-700
[77] Tamura Y, Peng P, Liu K, Daou M, Srivastava PK. Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science, 1997, 278(5335):117-119
[78] Bhattacharya-Chatterjee M, Chatterjee SK, Foon KA. Anti-idiotype antibody vaccine therapy for cancer. Expert Opin Biol Ther, 2002, 2(8): 869-881
[79] Alfonso M, Diaz A, Hernandez AM, Perez A, Rodriguez E, Bitton R, Perez R, Vazquez AM. An anti-idiotype vaccine elicits a specific response to N-gly-colyl sialic acid residues of glycoconjugates in melanoma patients. J Immunol, 2002, 168(5): 2523-2529
[80] Pervin S, Chakraborty M, Bhattacharya-Chatterjee M, Zeytin H, Foon KA, Chatterjee SK. Induction of antitumor immunity by an anti-idiotype antibody mimicking carci- noembryonic antigen. Cancer Res, 1997, 57 (4): 728-734
[81] Dillman RO. Monoclonal antigodies in the treatment of malignancy: basic concepts and recent developments. Cancer Invest, 2001, 19(8): 833-841
[82] Ligibel JA, Winer EP. Trastuzumab/chemotherapy combinations in metastatic breast cancer. Semin Oncol, 2002,29(3 Suppl 11): 38-43
[83] Coiffier B. Rituximab in combination with CHOP improves survival in elderly patients with aggressive non-Hodgkin's lymphoma. Semin Oncol, 2002, 29(2 Suppl 6): 18-22
[84] Francis RJ, Sharma SK, Springer C, Green AJ, Hope-Stone LD, Sena L, Martin J, Adamson KL, Robbins A, Gumbrell L, O'Malley D, Tsiompanou E, Shahbakhti H, Web-ley S, Hochhauser D, Hilson AJ, Blakey D, Begent RH. A phase I trial of antibody direc- ted enzyme prodrug therapy (ASEPT) in patients with colorectal carcinoma or other CEA producing tumours. Br J Cancer, 2002, 87(6): 600-607
[85] DeWeese TL, van der Poel H, Li S, Mikhak B, Drew R, Goemann M, Hamper U, DeJong R, Detorie N, Rodriguez R, Haulk T, DeMarzo AM, Piantadosi S, Yu DC, Chen Y, Henderson DR, Carducci MA, Nelson WG, Simons JW. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation therapy. Cancer Res, 2001, 61(20): 7464- 7472
[86] Whelan M, Whelan J, Russell N, Dalgleish A. Cancer immunotherapy: an embarrassment of riches? Drug Discov Today, 2003, 8(6): 253-258
[87] Baldwin RW. Immunity to methylcholanthrene-induced tumors in inbred rats following atrophy and implanted tumors. Br J Cancer, 1955,9: 652-665
[88] Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl Cancer Inst, 1957,18:769-778
[89] Klein G, Sjogren HO, Klein E, Hellstrom KE. Demonstration of resistance against methylcholanthrene-induced sarcomas in the primary autochthonous host. Cancer Res, 1960,20: 1561-1572
[90] Boon T, Coulie PG, Van den Eynde B.Tumor antigens recognized by T cells. Immunol Today, 1997, 18(6): 267-268
[91] van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991, 254(5038): 1643-1647
[92] Stevanovic S. Identification of tumor-associated T-cell epitopes for vaccine development. Nature Rev, 2002, 2: 1-7
[93] Chen YT, Scanlan MJ, Sahin U. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA, 1997,94: 1914-1918
[94] Gabrilovich DI, Nadaf S, Corak J, Berzofsky JA, Carbone DP. Dendritic cells in an- titumor immune responses. II. Dentritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors. Cell Immunol, 1996, 170 (1): 111-119
[95] Herin M, Lemoine C, Weynants P, Vessiere F, Van Pel A, Knuth A, Devos R, Boon T. Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int. J. Cancer, 1987, 39: 390-396
[96] Chomez P, De Backer O, Bertrand M, De Plaen E, Boon T, Lucas S. An overview of the MAGE gene family with the identification of all human members of the family. Cancer Res, 2001, 61(14): 5544-5551
[97] Dabovic B, Zanaria E, Bardoni B, Lisa A, Bordignon C, Russo V, Matessi C, Traversari C, Camerino G. A family of rapidly evolving genes from the sex reversal critical region in Xp21. Mamm. Genome, 1995, 6(9): 571-580
[98] Muscatelli F, Walker AP, De Plaen E, Stafford AN, Monaco AP. Isolation and characterization of a new MAGE gene family in the Xp21.3 region. Proc Natl Acad Sci USA,1995, 92(11): 4987-4991
[99] Lucas S, De Smet C, Arden KC, Viars CS, Lethe B, Lurquin C, Boon T. Identifica tion of a new MAGE gene with tumor-specific expression by representational difference analysis. Cancer Res, 1998, 58(4): 743-752
[100] Lucas S, De Plaen E, Boon T. MAGE-B5, MAGE-B6, MAGE-C2 and MAGE-C3: four new members of the MAGE family with tumor-specific expression, Int J Cancer, 2000, 87:55-60
[101] Lucas S, Brasseur F, Boon T. A new MAGE gene with ubiquitous expression does not code for known MAGE antigens recognized by T cells. Cancer Res, 1999, 59: 4100-4103
[102] Pold M, Zhou J, Chen GL, Hall JM, Vescio RA, Berenson JR. Identification of a new, unorthodox member of the MAGE gene family. Genomics, 1999, 59(2): 161-167
[103] Lurquin C, De Smet C, Brasseur F, Muscatelli F, Martelange V, De Plaen E, Brasseur R, Monaco AP, Boon T. Two members of the human MAGEB gene family located in Xp21.3 are expressed in tumors of various histological origins. Genomics, 1997, 46(3): 397-408
[104] Kawano Y, Sasaki M, Nakahira K, Yoshimine T, Shimizu K, Wada H, Ikenaka K. Structural characterization and chromosomal localization of the MAGE-E1 gene. Gene, 2001, 277(1-2): 129-137
[105] Fukuda MN, Sato T, Nakayama J, Klier G, Mikami M, Aoki D, Nozawa S. Trophinin and tastin, a novel cell adhesion molecule complex with potential involvement in embryo implantation. Gene Dev., 1995, 9: 1199-1210
[106] Suzuki N, Nadano D, Paria BC, Kupriyanov S, Sugihara K, Fukuda MN. Trophinin expression in the mouse uterus coincides with implantation and is hormoneally regulated but not induced by implanting blastocysts. Endocrinology, 2000, 141: 4247-4254
[107] De Plaen E, De Backer O, Arnaud D, Bonjean B, Chomez P, Martelange V, Avner P, Baldacci P, Babinet C, Hwang SY, Knowles B, Boon T. A new family of mouse genes homologous to the human MAGE genes. Genomics, 1999, 55: 176-184
[108] De Backer O, Verheyden AM, Martin B, Godelaine D, De Plaen E, Brasseur R, Avner P, Boon T. Structural, chromosomal location, and expression pattern of three mouse homologous to the human MAGE genes. Genomics, 1995, 28(1): 47-83
[109] Eura M, Chikamatsu K, Ogi K, Nakano K, Masuyama K, Ishikawa T. Expression of genes MAGE-1, -2, and -3 by human maxillary carcinoma cells. Anticancer Res, 1995, 15(1): 55-59
[110] Eura M, Ogi K, Chikamatsu K, Lee KD, Nakano K, Masuyama K, Itoh K, Ishikawa T. Expression of the MAGE gene Family in human head-and-neck squamous cell carcinomas. Int J Cancer, 1995, 64(5): 304-308
[111] Quillien V, Raoul JL, Heresbach D, Collet B, Toujas L, Brasseur F. Expression of MAGE genes in esophageals squamous cell carcinoma. Anticancer Res, 1997, 17(1A): 387-391
[112] Li J, Yang Y, Fujie T, Tanaka F, Mimori K, Haraguchi M, Ueo H, Mori M, Akiyoshi T. Expression of the MAGE gene family in human gastric carcinoma. Anticancer Res, 1997, 17(5A): 3559-3563
[113] Yoshimatsu T, Yoshino I, Ohgami A, Takenoyama M, Hanagiri T, Nomoto K, Yasumoto K. Expression of the melanoma antigen encoding gene in human lung cancer. J Surg Oncol, 1998, 67(2): 126-129
[114] Hasegawa H, Mori M, Haraguchi M, Ueo H, Sugimachi K, Akiyoshi T. Expression spectrum of melanoma antigen encoding gene family members in colorectal carcinoma. Arch Pathol Lab Med, 1998, 122(6): 551-554
[115] Tahara K, Mori M, Sadanaga N, Sakamoto Y, Kitano S, Makuuchi M. Expression of the MAGE gene family in human hepatocellular carcinoma. Cancer, 1999, 85(6): 1234-1240
[116] Chen YT, Stockert E, Chen Y, Garin-Chesa P, Rettig WJ, van der Bruggen P, Boon T, Old LJ. Identification of the MAGE-1 gene product by monoclonal and polyclonal an- tibodies. Proc Natl Acad Sci USA, 1994, 91(3): 1004-1008
[117] Kocher T, Schultz-Thater E, Gudat F, Schaefer C, Casorati G, Juretic A, Willimann T, Harder F, Heberer M, Spagnoli GC. Identification and intracellular location of MAGE-3 gene product. Cancer Res, 1995, 55(11): 2236-2239
[118] Shichijo S, Hayashi A, Takamori S, Tsunosue R, Hoshino T, Sakata M, Kuramoto T, Oizumi K, Itoh K. Detection of MAGE-4 protein in lung cancers. Int J Cancer, 1995, 64(3): 158-165
[119] 蔡胜利,冷希圣,杜如昱.肿瘤特异性抗原-MAGE家族的研究进展.中华外科杂志,2001,39(8):645-647
[120] Sasaki M, Nakahira K, Kawano Y, Katakura H, Yoshimine T, Shimizu K, Kim SU, Ikenaka K. MAGE-E1, a new member of the melanoma-associated antigen gene family and its expression in human glioma. Cancer Res, 2001, 61: 4809-4814
[121] Janssen BL, van de Locht LT, Fourkour A, de Smet C, Mensink EJ, van Muijen GN, de Vries TJ. Transcription of the MAGE-1 gene and the methylation status of its Ets binding promoter elements: a quantitative analysis in melanoma cell lines using a real time polymerase chain reaction technique. Melanoma Res, 1999, 9(3): 213-22
[122] Weber J, Salgaller M, Samid D, Johnson B, Herlyn M, Lassam N, Treisman J, Rosenberg SA. Expression of the MAGE-1 tumor antigen is upregulated by the demethylatingagent 5-aza-2'-deoxycytidine. Cancer Res, 1994, 54(7): 1766-1771
[123] Mori M, Inoue H, Mimori K, Shibuta K, Baba K, Nakashima H, Haraguchi M, Tsuji K, Ueo H, Barnard GF, Akiyoshi T. Expression of MAGE genes in human colorectal carcinoma. Ann Surg, 1996, 224(2): 183-188
[124] Shichijo S, Yamada A, Sagawa K, Iwamoto O, Sakata M, Nagai K, Itoh K. Induction of MAGE genes in lymphoid cells by the demethylatingagent 5-aza-2'-deoxycytidine. Jpn J Cancer Res, 1996, 87(7): 751-756
[125] De Smet C, Lurquin C, Lethe B, Martelange V, Boon T. DNA methylation is the primary silencing mechanism for a set of germline and tumor specific genes with a CpG rich promoter. Mol Cell Biol, 1999, 19(11): 7327-7335
[126] De Smet C, De Backer O, Faraoni I, Lurquin C, Brasseur R, Boon T. The activation of human gene MAGE-1 in tumor cells is correlated with genome-wide demethylation. Proc. Natl. Acad. Sci. USA, 1996, 93: 7149-7153
[127] Takahash K, Shichijo S, Noguchi M, Hirohata M, Itoh K. Identification of MAGE-1 and MAGE-4 protein in spernatogonia and primary spermaticytes of testis. Cancer Res, 1995, 55: 3478-3482
[128] Osterlund C, Tohomem V, Forslund KO, Nordqvist K. Mage-b4, a novel melanoma antigen(MAGE) gene specifically expressed during germ cell differentiation. Cancer Res, 2000, 60: 1054-1061
[129] Taniura H, Taniguchi N, Hara M, Yoshikawa K. Necdin, a postmiotic neron-specific growth suppressor, interacts with viral transforming proteins and cellular transcription factor E2F1. J Biol Chem, 1998, 273: 720-728
[130] Taniura H, Matsumoto K, Yoshikawa K. Physical and functionl interactions of neuronal growth suppressor necdin with p53. J Biol Chem, 1999, 274 (23): 16242-16248
[131] Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA. NRAGE, a novel MAGE protein, interacts with the p75 neuro-trophin receptor and facilitates nerve growthfactor-dependent apoptosis. Neuron, 2000, 27(2): 279-288
[132] Jordan BW, Dinev D, Le Mellay V, Troppmair J, Gotz R, Wixler, Sendtner M, Ludwig S, Rapp UR. Neurotrophin receptor-interacting Mage homoiogue is an inducible inhibitor of apoptosis protein-interacting protein thet augments cell death. J. Biol. Chem, 2001, 276(43): 39985-39989
[133] Scanlan MJ, Gure AO, Jungbluth AA, Old LJ, Chen YT. Cancer/testis antigens: an expanding family of targets for cancer immunotherapy. Immunol Rev, 2002, 188(1): 22-32
[134] Panelli MC, Bettinotti MP, Lally K, Ohnmacht GA, Li Y, Robbins P, Riker A, Rosenberg SA, Marincola FM. A tumor-infiltrating lymphocyte from a melanoma metastasis with decreased expression of melanoma differentiation an-tigens recognizes MAGE-12. J Immunol, 2000, 164(8): 4382-4390
[135] Gajewski TF, Fallarino F, Ashikari A, Sherman M. Immunization of HLA-A2+ melanoma patients with MAGE-3 or MelanA peptide-pulsed autologous peripheral blood mononuclear cells plus recombinant human interleukin 12. Clin Cancer Res, 2001, 7(3 Suppl): 895-901
[136] Serrano A, Lethe B, Delroisse JM, Lurquin C, De Plaen E, Brasseur F, Rimoldi D, Boon T. Quantitative evaluation of the expression of MAGE genes in tumors by limiting dilution of cDNA libraries. Int J Cancer, 1999, 83(5): 664-649
[137] Hillig RC, Coulie PG, Stroobant V, Saenger W, Ziegler A, Hulsmeyer M. High-resolution structure of HLA-A~*0201 in complex with a tumour-specific antigenic peptide encoded by the MAGE-A4 gene. J Mol Biol, 2001, 310(5): 1167-1176
[138] Heidecker L, Brasseur F, Probst-Kepper M, Gueguen M, Boon T, Van den Eynde BJ. Cytolytic T lymphocytes raised against a human bladder carcinoma recognize an antigen encoded by gene MAGE-A 12. J Immunol, 2000, 164(11): 6041-6045
[139] Jaeger E, Bernhard H, Romero P, Ringhoffer M, Arand M, Karbach J, Ilsemann C, Hagedorn M, Knuth A. Generation of cytotoxic T-cell responses with synthetic melanoma-associated peptides in vivo: implications for tumor vaccines with melanoma-associated antigens. Int J Cancer, 1996, 66(2): 162-169
[140] Graff-Dubois S, Faure O, Gross DA, Alves P, Scardino A, Chouaib S, Lemonnier FA, Kosmatopoulos K. Generation of CTL recognizing an HLA-A~*0201-restricted epitope shared by MAGE-A1, -A2, -A3, -A4, -A6, -A10, and -A12 tumor antigens: implication in a broad-spectrum tumor immunotherapy. J Immunol, 2002, 169(1): 575-580
[141] Marchand M, Punt CJ, Aamdal S, Escudier B, Kruit WH, Keilhoiz U, Hakansson L, van Baren N, Humblet Y, Mulders P, Avril MF, Eggermont AM, Scheibenbogen C, Uiters J, Wanders J, Delire M, Boon T, Stoter G. Immunization of metastatic cancer patients with MAGE-3 protein combined with adjuvant SBAS-2: a clinical report. Eur J Cancer, 2003, 39(1): 70-77
[142] Hoon DS, Yuzuki D, Hayashida M, Morton DL. Melanoma patients immunized with melanoma cell vaccine induce antibody responses to recombinant MAGE-1 antigen. J Immunol, 1995, 154(2): 730-737
[143] Reynolds SR, Oratz R, Shapiro RL, Hao P, Yun Z, Fotino M, Vukmanovic S, Bystryn JC. Stimulation of CD8+ T cell responses to MAGE-3 and Melan A/MART-1 by immunization to a polyvalent melanoma vaccine. Int J Cancer, 1997, 72(6): 972-976
[144] Tjandrawan T, Martin DM, Maeurer MJ, Castelli C, Lotze MT, Storkus WJ. Autologous human dendriphages pulsed with synthetic or natural tumor peptides elicit tumor specific CTLs in vitro. J Immunother, 1998, 21(2): 149-157
[145] Sadanaga N, Nagashima H, Mashino K, Tahara K, Yamaguchi H, Ohta M, Fujie T, Tanaka F, Inoue H, Takesako K, Akiyoshi T, Mori M. Dendritic cell vaccination with MAGE peptide is a novel therapeutic approach for gastrointestinal carcinomas. Clin Cancer Res, 2001, 7(8): 2277-2784
[146] Berard F, Blanco P, Davoust J, Neidhart-Berard EM, Nouri-Shirazi M, Taquet N, Rimoldi D, Cerottini JC, Banchereau J, Palucka AK. Cross-priming of naive CD8 T cells against melanoma antigens using dendritic cells loaded with killed allogeneic melanoma cells. J Exp Med, 2000, 192(11): 1535-1544
[147] Tuting T, Wilson CC, Martin DM, Kasamon YL, Rowles J, Ma DI, Slingluff CL Jr, Wagner SN, van der Bruggen P, Baar J, Lotze MT, Storkus WJ. Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha. J Immunol, 1998, 160(3): 1139-1147
[148] Bueler H, Mulligan RC, Induction of antigen specific tumor immunity by genetic and cellular vaccines against MAGE: enhanced tumor protection by coexpression of granulocyte macrophagecolony stimulating factor and B7.1. Mol Med, 1996, 2(5): 545-555
[149] Sun X, Hodge LM, Jones HP, Tabor L, Simecka JW. Co-expression of granulocyte-macrophage colony-stimulating factor with antigen enhances humoral and tumor immunity after DNA vaccination. Vaccine, 2002, 20(9-10): 1466-1474
[150] Hoon DS, Wang Y, Dale PS, Conrad AJ, Schmid P, Garrison D, Kuo C, Foshag LJ, Nizze A J, Morton DL. Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay. J Clin Oncol, 1995, 13(8): 2109-2016
[151] Iwamoto O, Nagao Y, Shichijo S, Eura M, Kameyama T, Itoh K. Detection of MAGE-4 protein in sera of patients with head-and-neck squamous-cell carcinoma. Int J Cancer, 1997, 70(3): 287-290
[152] Liu BB, Ye SL, He P, Liu YK, Tang ZY. MAGE-1 and related MAGE gene expression may be associated with hepatocellular carcinoma. J Cancer Res Clin Oncol, 1999, 125(12): 685-689
[153] 蔡胜利,陈红松,王瑜,赵海涛,彭吉润,庞学文,龚顺友,朱继业,丛旭,王宇,芮静安,冷圣希,杜如昱,陈慰峰.黑色素瘤抗原-1基因在肝细胞癌中的表达.中华医学杂志,1999,79:668-671
[154] 武文,隋延仿,叶菁,等.人肝癌细胞系中肿瘤相关基因MAGE的克隆.细胞与分子免疫学杂志,2002,18:270-274
[155] 董海龙,随延仿,叶菁,李增山,曲萍,张秀敏,陈广生,禄韶英.肿瘤抗原MAGE-n HLA-A2限制性细胞毒性T细胞表位的预测及合成鉴定.中华医学杂志,2003,83(11):1-4
[156] Hailong Dong, Yanfang Sui, Zengshan Li, Ping Qu, Wen Wu, Jing Ye, Xiumin Zhang, Shaoying Lu. Efficient induction of cytotoxic T lymphocytes specific to heaptocellular carcinoma using HLA-A2-restricted MAGE-n peptide in vitro. Cancer Letter, 2004, 211: 219-225
[157] Tighe H, Corr M, Roman M, Raz E. Gene vaccination: plasmid DNA is more than just a bluerint. Immunol Today, 1998, 19(2): 89-97
[158] Levitsky HI. Accessories for naked DNA vaccines. Nat Biotechnol, 1997, 15(7): 619-620
[159] Reimann J, Kaufmann SH. Alternative antigen processing pathways in anti-infective immunity. Curr Opin Immunol, 1997, 9(4): 462-469
[160] Stenger S, Modlin RL. Cytoxic T cell responses to intracellular pathogens. Curr Opin Immunol, 1998, 10(4): 471-477
[161] Reise Sousa C, Sher A, Kaye P. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Ocrr Opin Immunol, 1999, 11(4): 392-399
[162] Gustafsson J, Arvidson G, Karlsson G, Almgren M. Complexes between cationic liposomes and DNA visualized by cryo-TEM. Biochim Biophys Acta, 1995, 1235(2): 305-312
[163] Farthood H, Serbina N, Huang L. The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. Biochim Biophys Acta, 1995, 1235(2): 289
[164] Pinnaduwage P, Schmitt L, Huang L. Use of a quaternary ammonium detergent in liposome mediated DNA transfection of mouse L cells. Biochim Biophys Acta, 1989, 985(1): 33
[165] Gao X, Huang L. A novel cationic liposome reagent for efficient transfection in mammalian cells. Biochem Biophys Res Commun,1991, 179(1): 280
[166] Felgner PL, Ringold GM. Cationic liposomes-mediated transfection. Nature, 1989, 337(6205): 387
[167] Radler JO, Koltover I, Salditt T, Safinya CR. Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science, 1997, 275(5301): 810-814
[168] Nily D. Multilamellar structures of DNA complexes with cationic liposomes. Biophys J, 1997, 73(4): 1842-1846
[169] Spector MS, Schnur JM. DNA ordering on a lipid membrane. Science, 1997, 275 (5301): 791-792
[170] Farhood H, Gao X, Barsoum J, Huang L. Codelivery mammalian cells of a transcriptional factor with cis-acting element using cationic liposomes. Anal Biochem, 1995, 225(1): 89-93
[171] Hofland H, Huang L, Inhibition of human ovarian carcinoma cell proliferation by liposome-plasmid DNA complex. Biochem Biophys Res Commun, 1995, 207(2): 492
[172] 卢大儒,邱信芳,薛京伦.基因治疗转移方法的研究进展.国外医学·遗传学分册,1996,19(1):1
[173] Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, Huang L, Shu S, Gordon D, Chang AE. Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity and lack of toxicity in human. Proc Natl Acad Sci USA, 1993, 90(23): 11307-11311
[174] 王军志,丁锡申.国外基因治疗临床研究动向及市场展望.生物工程进展,1997,17(3):56
[175] Yoshida J, Mizuno M. Simple method to prepare cationic multilamellar liposomes for efficient transfection of human interferon-beta gene to human glioma cells. J Neurooncal, 1994, 19(3): 269
[176] 陈敏亮,林子豪,曹雪涛,王全兴,于益之,朱晓海,赵耀中,刘麒,袁相斌.鳞癌瘤体内注射脂质体包裹的人α干扰素基因的抗肿瘤治疗.第二军医大学学报,2000,21(11):1068-1070
[177] 王克敏,赵宇,张景迎,夏爱娣,陈诗书.阳离子脂质体介导细胞因子基因对小鼠肝癌抑制的作用.上海第二医科大学学报,1999,6(19):504-507
[178] Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature, 1995, 374(6522): 546-549
[179] Krieg AM, Roman M. Mechanisms and applications of immunostimulatory CpG oligodeoxynucleotides. Biochimica et Biophysica Acta, 1999, 1949:107
[180] Lipford GB, Bauer M, Blank C, Reiter R, Wagner H, Heeg K. CpG-containing synthetic oligonucleotides promote B and cytotoxic T cell responses to protein antigen. Eur J Immunol, 1997, 27(9): 2340-2344
[181] Yi AK, Hornbeck P, Lafrenz DE, Krieg AM. CpG DNA rescue of murine B lym- phoma cells from anti-IgM-induced growth arrest and programmed cell death is associated with increased expression of c-myc and bcl-xL. J Immunol, 1996, 157(11): 4918- 4925
[182] Yi AK, Krieg AM. CpG DNA rescue from anti-IgM-induced WEIHI-231 B lympho-ma apoptosis via modulation of I kappa B alpha and I kappa N beta and sustained activation of nuclear factor-kappa B/c-Rel. J Immunol, 1998, 160 (3): 1240-1245
[183] Sparwasser T, Koch ES, Vabulas RM, Heeg K, Lipford GB, Ellwart JW, Wagner H. Bacterial DNA and immunostimulatory CpG oligonucleotides trigger maturation and activation of murine dendritic cells. Eur J Immunol, 1998,28(6): 2045-2054
[184] Ballas ZK, Rasmussen WL, Krieg AM. Induction of NK activity in murine and human cells by CpG motifs in oligodeoxynucleotides and bacterial DNA. J Immunol, 1996, 157(5): 1840-1845
[185] Chace JH, Hooker NA, Mildenstein KL, Krieg AM, Cowdery JS. Bacterial DNA-nduced NK cell IFN-gamma production is dependent on macrophage secretion of IL-12. Clin Immunol Immunopathol, 1997, 84(2): 185-193
[186] Halpern MD, Kurlander RJ, Pisetsky DS. Bacterial DNA induces murine interferon-gamma production by stimulation of interleukin-12 and tumor necrosis factor-alpha. Cell Immunol, 1996, 167(1): 72-78
[187] Bendigs S, Salzer U, Lipford GB, Wagner H, Heeg K. CpG-oligodeoxynucleotides costimulate primary T cells in the absence of antigen presenting cells. Eur J Immunol, 1999,29(4): 1209-1218
[188] Oxenius A, Martinic MM, Hengartner H, Klenerman P. CpG-containing oligonucleotides are efficient adjuvants for induction of protective antiviral immune responses with T cell peptide vaccines. J Virol, 1999, 73(5): 4120-4126
[189] Yi AK, Krieg AM. Rapid induction of Mitogen-activated protein kinases by immune stimulatory CpG DNA. J Immunol, 1998, 161:4493
[190] Yi AK, Tuetken R, Redford T, Waldschmidt M, Kirsch J, Krieg AM. CpG motifs in bacterial DNA activate leukocytes through the pH-dependent generation of reactive oxygen species. J Immunol, 1998, 160(10): 4755-61
[191] Hacker H. Signal transduction pathways activated by CpG-DNA. Curr Top Mcro-biol Immunol, 2000, 247: 77
[192]Macfarlane DE, Manzel L. Antagonism of immunostimulatory CpG-oligodeoxynucleotides by quinacrine, chloroquine, and structurally related compounds. J Immonol,1998, 160(3): 1122-1131
[193] Weiner GJ, Liu HM, Wooldridge JE, Dahle CE, Krieg AM. Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization. Proc Natl Acad Sci USA, 1997, 94(20): 10833-10837
[194] Wooldridge JE, Ballas Z, Krieg AM, Weiner GJ. Immunostimulatory oligodeoxynucleotides containing CpG motifs enhance the efficacy of monoclonal antibody therapy of lymphoma. Blood, 1997, 89(8): 2994-2998
[195] Schlossman SF, Boumsell L, Gilks W, Harlan JM, Kishimoto T, Morimoto C, Ritz J, Shaw S, Silverstein RL, Springer TA. CD antigens 1993. Immu- nol Today, 1994, 15(3): 98-99
[196] Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, Banche-reau J. B70/B7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med, 1994, 180(5): 1841-1847
[197] Boussiotis VA, Freeman GJ, Gribben JG, Nadler LM. The role of B7-1/ B7-2: CD28/CLTA-4 pathways in the prevention of anergy, induction of productive immunity and down-regulation of the immune response. Immunol Rev, 1996, 153: 5-26
[198] Thurnher M, Radmayr C, Hobisch A, Bock G, Romani N, Bartsch G, Klocker H. Tumor-infiltrating T lymphocytes from renal-cell carcinoma express B7-1 (CD80): T-cell expansion by T-T cell co-stimulation. Int J Cancer, 1995,62(5): 559-564
[199] Pichler WJ, Tony Wyss Coray. T cells as antigen-presenting cells. Immunol Today, 1994,15(7): 312-315
[200] Denfeld RW, Dietrich A, Wuttig C, Tanczos E, Weiss JM, Vanscheidt W, Schopf E, Simon JC. In situ expression of B7 and CD28 receptor families in hu- man malignant melanoma: relevance for T-cell-mediated anti-tumor immunity. Int J Cancer, 1995,62(3): 259-265
[201] Chen L, Ashe S, Brady WA, Hellstrom I, Hellstrom KE, Ledbetter JA, McGowan P, Linsley PS. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell, 1992, 71 (7): 1093-1102
[202] Mochizuki K, Hayashi N, Katayama K, Hiramatsu N, Kanto T, Mita E, Tatsumi T, Kuzushita N, Kasahara A, Fusamoto H, Yokochi T, Kamada T. B7/ BB-1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C. Hepatology, 1997, 25 (3): 713-718
[203] Tatsumi T, Takehara T, Katayama K, Mochizuki K, Yamamoto M, Kanto T, Sasaki Y, Kasahara A, Hayashi N. Expression of costimulatory molecules B7-1 (CD80) and B7- 2 (CD86) on human hepatocellular carcinoma. Hepatology, 1997, 25(5): 1108-1114
[204] Pettit SJ, Ali S, O'Flaherty E, Griffiths TR, Neal DE, Kirby JA. Bladder cancer im- munogenicity: expression of CD80 and CD86 is insufficient to allow primary CD4+ T cell activation in vitro. Clin Exp Immunol, 1999,116(1): 48-56
[205] Hideki F, Manabu I, Fuminari K, Jun M, Masaaki M, Yasuharn O, Ichiro A, Toshi- mitsu U Ikuo S. Vaccination of tumor transfected with the B7-l(CD80) Gene induces the anti-metastatic effect and tumor immunity in mice. Int J Cancer, 1996, 66: 219-224
[206] Gaken JA, Hollingsworth SJ, Hirst WJ, Buggins AG, Galea-Lauri J, Peakman M, Kuiper M, Patel P, Towner P, Patel4 PM, Collins MK, Mufti GJ, Farzaneh F, Darling DC. Irradiated NC adenocarcinoma cells transduced with both B7.1 and interleukin-2 induce CD4+-mediated rejection of established tumors. Hum Gene Ther, 1997, 8(4): 477-488
[207] Kato K, Okumura K, Yagita H. Immunoregulation by B7 and IL-12 gene transfer. Leukemia, 1997, 11(Suppl 3): 572-576
[208] Putzer BM, Hitt M, Muller WJ, Emtage P, Gauldie J, Graham FL. Interleukin 12 and B7-1 costimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regression. Proc Natl Acad Sci USA, 1997, 94 (20): 10889-10894
[209] Cayeux S, Beck C, Dorken B, Blankenstein T. Coexpression of interleukin-4 and B7.1 in murine tumor cells leads to improved tumor rejection and vaccine effect compared to single gene transfectants and a classical adjuvant. Hum Gene Ther, 1996, 7(4): 525-529
[210] Parney IF, Petruk KC, Zhang C, Farr-Jones M, Sykes DB, Chang LJ. Granulocyte- macrophage colony-stimulating factor and B7-2 combination immunogene therapy in an allogeneic Hu-PBL-SCID/beige mouse-human glioblastoma multiforme model. Hum Gene Ther, 1997; 8(9):1073-1085
[201] Yang S, Vervaert CE, Seigler HF, Darrow TL. Tumor cells cotransduced with B7.1 and gamma-IFN induce effective rejection of established parental tumor. Gene Ther, 1999; 6(2): 253-262
[212] Pulaski BA, Ostrand-Rosenberg S. Reduction of established spontaneous mammary carcinoma metastases following immunotherapy with major histocompatibility complex class Ⅱ and B7.1 cell-based tumor vaccines. Cancer Res, 1998, 58(7): 1486-1493
[213] Zajac P, Schutz A, Oertli D, Noppen C, Schaefer C, Heberer M, Spagnoli GC, Marti WR. Enhanced generation of cytotoxic T lymphocytes using recombinant vaccinia virus expressing human tumor-associated antigens and B7 costimulatory molecules. Cancer Res, 1998; 58(20): 4567-4571
[214] Imro MA, Dellabona P, Manici S, Heltai S, Consogno G, Bellone M, Rugarli C, Protti MP. Human melanoma cells transfected with the B7-2 co-stimulatory molecule induce tumor-specific CD8+ cytotoxic T lymphocytes in vitro. Hum Gene Ther, 1998, 9(9): 1335-1344
[215] Cayeux S, Richter G, Becker C, Beck C, Aicher A, Pezzutto A, Dorken B, Blankenstein T. Lack of correlation between rejection of tumor cells co-expressing interleukin-2 and B7.1 and vaccine efficiency. Eur J Immunol, 1997, 27(7): 1657-1662
[216] Musgrave BL, Phu T, Butler JJ, Makrigiannis AP, Hoskin DW. Murine TRAIL (TNF-related apoptosis inducing ligand) expression induced by T cell activation is blocked by Rapamycin, cyclosporin A, and inhibitors of phosphatidylinositol 3-kinase, protein kinase C, and protein tyrosine kinase: evidence for TRAIL induction via the T cell receptor signaling pathway. Exp Cell Res, 1999, 252(1): 96-103
[217] 李春英,高天文.恶性黑素瘤核酸疫苗免疫影响因素及对策.国外医学皮肤性病学分册,2001,27(5):288-290
[218] Itoh K, Hayashi A, Nakao M, Hoshino T, Seki N, Shichijo S. Human tumor rejecttion antigens MAGE. J Biochem Tokyo, 1996, 119(3): 385-390
[219] Mukherji B, Chakraborty NG, Yamasaki S, Okino T, Yamase H, Sporn JR, Kurtzman SK, Ergin MT, Ozols J, Meehan J. Induction of antigen-specific cytolytic T cells in situ in human melanoma by immunization with synthetic peptide-pulsed autologous antigen presenting cells. Proc Natl Acad Sci U S A, 1995, 92 (17): 8078-8082
[220] Lu J, Leng X, Peng J, Mou D, Pang X, Shang X, Chen W. Induction of cytotoxic T lymphocytes from the peripheral blood of a hepatocellular carcinoma patient using melanoma antigen-1 (MAGE-1) peptide. Chin Med J (Engl), 2002, 115(7): 1002-1005
[221] Ye J, Chen GS, Song HP, Li ZS, Huang YY, Qu P, Sun YJ, Zhang XM, Sui YF. Heatshock protein 70/MAGE-1 tumor vaccine can enhance the potency of MAGE-1-specific cellular immune responses in vivo. Cancer Immunol Immuno Ther, 2004, 53(9): 825-834
[222] Ma JH, Sui YF, Ye J, Huang YY, Li ZS, Chen GS, Qu P, Song HP, Zhang XM. Heat shock protein 70/MAGE-3 fusion protein vaccine can enhance cellular and humoral im mune responses to MAGE-3 in vivo. Cancer Immunol Immunother, 2005, Mar 9, in pub lication
[223] Hurwitz AA, Townsend SE, Yu TF, Wallin JA, Allison JP. Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma. Int J Cancer, 1998, 77(1): 107-113
[224] Vasilevko V, Ghochikyan A, Sadzikava N, Petrushina I, Tran M, Cohen EP, Kesslak PJ, Cribbs DH, Nicolson GL, Agadjanyan MG. Immunization with a vaccine that combines the expression of MUC 1 and B7 co-stimulatory molecules prolongs the survival of mice and delays the appearance of mouse mammary tumors. Clin Exp Metastasis, 2003, 20(6): 489-98
[225] Disis ML, Scholler N, Dahlin A, Pullman J, Knutson KL, Hellstrom KE, Hellstrom I. Plasmid-based vaccines encoding rat neu and immune stimulatory molecules can elicit rat neu-specific immunity. Mol Cancer Ther, 2003, 2(10): 995-1002