骨肉瘤细胞与巨噬细胞融合诱导主动性抗肿瘤免疫效应的研究
|
摘要
随着肿瘤研究的不断深入，传统的手术方法有了很大改进，使得骨肉瘤的局部控制成为可能。然而，尽管联合了化疗和放疗，仍有大约40％的患者发生肺转移，成为治疗失败的主要原因。
以CTL识别为基础的技术路线的建立，使人们在多种肿瘤中发现了新的抗原，尤其是黑色素瘤MAGE、MART等抗原的发现，极大地促进了主动性免疫治疗的发展，数个治疗方案已经进入临床试验阶段，以主动性免疫治疗为主的生物治疗正日益成为一种新的有效治疗手段，但遗憾的是目前尚未在骨肉瘤中找到类似的CTL识别抗原用于主动性免疫治疗。
为了提高骨肉瘤细胞的免疫原性，本研究采用专业的抗原提呈细胞巨噬细胞与骨肉瘤细胞融合的技术路线，探讨融合瘤苗在
Along with the development of cancer research, the traditional operation scheme have been changed in many ways, that makes the local control of osteosarcoma become possible. But the almost 40% lung metastasis tends to result in treatment failure in spite of combined with radiotherapy and chemotherapy.
The findings of tumor specific antigen recognized by CTL, especially the melanoma antigens MAGE and MART, have promoted the active immunotherapy in large extent and then several clinical trails are in progress. The immunotherapy based on a greater appreciation of the mechanisms by which tumor-specific cytolytic cells are generated is becoming a new approach in cancer treatment.
Central to the induction of CTL responses are professional antigen-presenting cells, including macrophages and dendritic cells, which present tumor antigen to the immune system in the context of major
以CTL识别为基础的技术路线的建立，使人们在多种肿瘤中发现了新的抗原，尤其是黑色素瘤MAGE、MART等抗原的发现，极大地促进了主动性免疫治疗的发展，数个治疗方案已经进入临床试验阶段，以主动性免疫治疗为主的生物治疗正日益成为一种新的有效治疗手段，但遗憾的是目前尚未在骨肉瘤中找到类似的CTL识别抗原用于主动性免疫治疗。
为了提高骨肉瘤细胞的免疫原性，本研究采用专业的抗原提呈细胞巨噬细胞与骨肉瘤细胞融合的技术路线，探讨融合瘤苗在
Along with the development of cancer research, the traditional operation scheme have been changed in many ways, that makes the local control of osteosarcoma become possible. But the almost 40% lung metastasis tends to result in treatment failure in spite of combined with radiotherapy and chemotherapy.
The findings of tumor specific antigen recognized by CTL, especially the melanoma antigens MAGE and MART, have promoted the active immunotherapy in large extent and then several clinical trails are in progress. The immunotherapy based on a greater appreciation of the mechanisms by which tumor-specific cytolytic cells are generated is becoming a new approach in cancer treatment.
Central to the induction of CTL responses are professional antigen-presenting cells, including macrophages and dendritic cells, which present tumor antigen to the immune system in the context of major
引文
1. Rosenberg SA, Packard BS, Aebersold PM et al. Use of tumor infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. Preliminary report. N Engl J Med, 1988;319:1676-1680
2. Rosenberg SA. The immunotherapy and gene therapy of cancer. J Clin Oncol 1992;10:180-199
3. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes Science 1986;233:1318-1321
4. Kast WM, Offringa R, Peters PJ et al. Eradication of adenovirus E1-induced tumors by E1A specific cytotoxic T lymphocytes. Cell,1989;59:603-614
5. Greenbeerg PD. Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv Immunol 1991;49:281-355
6. Disis ML, Cheever MA. HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Adv Cancer Res 1992;21:343-71
7. Apostolopoulos V, McKenzie IF, Pietersz GA et al. Breast cancer immunotherapy : current status and future prospects. Immunol Cell Biol 1996;74:457-64
8. Van den Eynde B, Van der Bruggen P. T cell-defined tumor antigens. Curr Opin Immunol 1997;9:684-693
9. Muul LM, Spiess PJ, Director EP et al. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol, 1987;138:989-95
10.Itoh K, Platsoucas CD, Balch CM. Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas: activation by interleukin 2 and autologous tumor cells,and involvement of the T cell receptor. J Exp Med 1988;168:1419-41
11. Belldegrun A, Kasid A, Uppenkamp M, et al. Human tumor infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. J Immunol,1989;142:4520-6
12. O'Neil BH, Kawakami Y, Restifo NP et al. Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. J Immunol,1993;151:1410-18
13. Peoples GE, Goedegebuure PS, Andrews JV et al. HLA-A2 presents shared tumor-associated antigens derived from endogenous proteins in ovarian cancer. J Immunol 1993;151:5481-91
14. Ioannides CG, PlatsoucasCD, Rashed S, et al. Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites. Cancer Res 1991;51:4257-65
15. Hom SS, Rosenberg SA, Topalian SL. Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas: analysis by cytokine secretion. Cancer Immunol Immunother 1993;36:1-8
16. Schwartzentruber DJ, Solomon D, RosenbergSA, et al.Characterization of lymphocytes infiltrating human breast cancer:specific immune reactivity detected by measuring cytokine secretion. J Immunother 1992;12:1-12
17. Schendel DJ, Gansbacher B, Oberneder R, et al. Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. 1. HLA-A2-restricted recognition ofautologous and allogeneic tumor lines. J Immunol 1993;151:4209-20
18. Kawakami Y, Eliyahu S, Delgado CH, et al. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci USA 1994;91:6458-62
19. Kawakami Y, Elyyahu S, Delgado CH, et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci USA 1994;91:3515-9
20. Robbins PF, El-Gamil M, Kawakami Y, et al.Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy Cancer Res 1994;54:3124-6
21. Wang RF, Robbin PF, Kawakami Y, et al. Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31- restricted tumor infiltrating lymphocytes. J Exp Med 1995;181:799-804
22. Coulie P, Brichard V, Van Pel A, et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1995;190:1-4
23. Brichard V, Van Pel A, Wolfel T et al. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-H2 melanomas. J Exp Med, 1993; 178:489-495
24. Bakker AB, Schreurs MW, de Boer AJ et al. Melanocyte lineage-specific antigen gp100 is recognized by melanocyte-derived tumor-infiltrating lymphocytes. J Exp Med, 1994; 179:1005-1009
25. Wang RF, Appella E, Kawakami Y, et al. Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.J Exp Med 1996;184:2207-2216
26. Van der Bruggen P, Traversari C, Chomez P et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991;254:1643-47
27. Van der Bruggen P, Bastin J, Gajewski T et al. A peptide encoded by human gene GAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur J Immunol, 1994;24:3038-3043
28. Herman J, Van der Bruggen P, Luescher IF et al. A peptide encoded by the human MAGE3 gene and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3. Immunogenetics, 1996;43:377-383
29. Boel P, Wildmann C, Sensi ML et al. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity, 1995;2:167-175
30. Van Den Eynde B, Peeters 0, De Backer O, et al. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 1995;182:689-698
31. Chen YT, Scanlan MJ, Sahin U et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA, 1997;94:1914-1918
32. Jager E, Chen YT, Drijfhout JW et al. Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen(HLA)-A2-binding peptide epitopes. J Exp Med, 1998;187:265-270
33. Wang RF, Johnston SL, Zeng G et al. A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames. J Immunol,1998;161:3596-3606
34. Gaugler B, Brouwenstijn N, Vantomme V et al. A new gene coding for an antigen recognized by autologous cytolytic T lymphocytes on a human renal carcinoma. Immunogenetics,1996;44:323-330
35. Ioannides CG, Fisk B, Pollack MS et al. Cytotoxic T-cell clones isolated from ovarian tumour infiltrating lymphocytes recognize common determinants on nonovarian tumour clones. Scand j Immunol, 1993;37:413-424
36. Yoshino I, Peoples GE, Geoedegebauure PS et al. Association of HER2/neu expression with sensitivity to tumor-specific CTL in human ovarian cancer. J Immunol, 1994;152:2393-2400
37. Disis ML, Calenoff E, McLaughlin G et al. Existent T cell and antibody immunity to HER-2/neu protein in patients with brease cancer. Cancer Res, 1994;54:16-20
38. Peoples GE, Goedegebuure PS, Smith R et al. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci USA,1995;92:432-436
39. Linehan DC, Goedegebuure PS, peoples GE et al. Tumor-specific and HLA-A2-restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer. J Immunol,1995; 155:4486-4491
40. Ioannides CG, Fisk B, Jerome KR et al. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol, 1993;151:3693-3703
41. Magarian-Blander J, Domenech N, Finn OJ. Specific and effective T-cell recognition of cells transfected with a truncated human mucin cDNA. Ann NY Acad Sci 1993;690:231-243
42. Finn OJ, Jerome KR, Henderson RA et al. MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev,1995;145:61-89
43. Apostolopoulos V, Karanikas V, Haurum JS et al. Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J Immunol 1997;159:5211-5218
44. Coulie PG, Lehmann F, Lethe B et al. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc natl Acad Sci USA,1995;92:7976-7980
45. Wolfel T, Hauer M, Schneider J et al. A p16-INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science, 1995;269:1281-1284
46. Mandruzzato S, Brasseur F, Andry G et al. A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma. J Exp Med, 1997;186:785-793
47. Robbins PF, E1-Gamil M, Li YF et al. A mutated β -catenin gene encodes a melanoma-spicific antigen recognized by tumor infiltrating lymphocytes. J Exp Med, 1996; 183:1185-1192
48. Kawanishi J, Kato J, Sasaki K et al. Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the β -catenin gene in a human cancer cell line, HSC-39. Mol Cell Biol, 1995;15:1175-1181
49. Korinek V, Barker N, Morin PJ et al. Constitutive transcriptional activation by a β -catenin-Tcf complex in APC-/- colon carcinoma. Science, 1997;275:1784-1787
50. Morin PJ, Sparks AB, Korinek V et al. Activation of β -catenin-Tcf signaling in colon cancer by mutations in betacatenin or APC.Science, 1997;275:1787-1790
51. Rubinfeld B, Robbins P, E1-Gamil M, et al. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997;275:1790-1792
52. Ostrand-Rosenberg S. Tumor immunotherapy: the tumor cell as an antigen-presenting cell. Curr Opin Immunol 1994;6:722-727
53. Pardoll DM, Topalian S. The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol 1998;10:588-594
54. Toes RE, Ossendorp F, Offringa R et al. CD4+ T cells and their role in antitumor immune responses. J Exp Med, 1999;189:753-756
55. Greenberg PD, Cheever MA, Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J Exp Med 1981 ;154:952-963
56. Schild HJ, Kyewski B, Von Hoegen P et al. CD4+ helper T cells are required for resistance to highly metastatic murine tumor. Eur j Immunol 1987;17:1863-1866
57. Romerdahl CA, Kripke ML. Role of helper T-lymphocytes in rejection of UV-induced murine skin cancers. Cancer Res 1988;48:2325-2328
58. Hung K, Hayashi R, Lafond-Walker A et al. The central role of CD4+ T cells in the antitumor immune response. J Exp Med 1998;188:2357-2368
59. Frasca L, Piazza C, Piccolella E. CD4+ T cells orchestrate both amplification and deletion of CD8+ T cells. Crit Rev Immunol 1998;18:569-594
60. Topalian SL, Rivoltini L, Mancini M et al. Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene. Proc Natl Acad Sci USA,1994;91:9461-9465
61. Topalian SL, Gonzales MI, Parkhurst M et al. Melanoma-specific CD4+ T cell recognize nonmutated HLA-DR- restricted tyrosinase epitopes. J Exp Med, 1996; 183:1965-1971
62. Haider T, Pawelec G, Kirkin AF et al. Isolation of novel HLA-DR restricted potential tumor-associated antigens from the melanoma cell line FM3. Cancer Res, 1997;57:3238-3244
63. Chaux P, Vantomme V, Stroobant V et al. Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4+ T lymphocytes. J Exp Med, 1999; 189:767-778
64. Manici S, Sturniolo T, Imro MA et al. Melanoma cells present a MAGE-3 epitope to CD4+ cytotoxic T cells in association with histocompatibility leukocyte antigen DR11. J Exp Med,1999;189:871-876
65. Pieper R, Christian RE, Genzales MI et al. Biochemical identification of a mutated human melanoma antigen recognized by CD4+ T cells. J Exp Med, 1999; 189:757-766
66. Wang RF, Wang X, Atwood AC et al. Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumour antigen. Science, 1999;284:1351-1354
67. Gareia Plata D, Mozos E, Sierra MA et al. HLA expression in basal cell carcinomas. Invasion Metastasis, 1991;11:166
68. Nouri AM, dos Santos AV, Crosby 0 et al. Correlation between class I antigen expression and the ability to generate tumour infiltrating lymphocytes from bladder tumour biopsies. Br j Cancer, 1991;64:996
69. Pardoll DM. Cancer vaccines. Immunol Today, 1993;14:310-316
70. Chamberlain RS, Carroll MW, Bronte V et al. Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines. Cance Res 1996;56:2832-6
71. McArthur JG, Raulet DH. CD28-induced costimulation of T helper type 2 cells mediated by induction responsiveness to interleukin 4. J Exp Med, 1993; 178:1645-53
72. Ramarathinam L, Castle M, Wu Y et al. T cell costimulation by B7/BBI induces CD8 T cell-dependent tumor rejection: an importment role of B7/BBI in the induction, recruitment, and effector function of antitumor T cells. J Exp Med, 1994;179:1025-1114
73. Chen L, Ashe, Brudy WA. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell, 1992;71:1093-l 102
74. Townsend SE, Allison JP. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells.Science, 1993;259:368-370
75. Li Y, McGowan P, Hellstrom I et al. Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J Immunol, 1994;153:421-8
76. Fenton RT, Sznol M, Kuster DG et al. A phase I trial of B7-transfected of parental lethally irradiated allogeneic melanoma cell lines to induce cell-mediated immunity against tumor-associated antigen presented by HLA-A2 or HLA-A1 in patients with stage IV melanoma. Human Gene Therapy, 1995;6:87-106
77. Pardoll D. Paracrine cytokine adjuvants in cancer immunotherapy.Annu Rev Immunol 1995;13:399-415
78. Golumbek PT, Lazenby AJ, Levitsky HI et al. Treatment of established renal cancer by tumor cell engineered to secrete interleukin-4. Science, 1991;254:713-716
79. Restifo NP, Spiese PJ, Karp SE et al. A nonimmunogenic sarcoma transducted with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability. J Exp Med, 1992:175:1423-1431
80. Colombo MP, Modesti A, Parmiani G et al. Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T- lymphocyte cross-talk. Cancer Res, 1992;52:4853-4857
81. Hock H, Dorsch M, Diamantstein T et al. Interleukin T induces CD4+ T cell-dependent tumor rejection. J Exp Med,1991;174:1291-1298
82. Colombo M, Forni G . Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 1994;15:48-51
83. Fearon ER, Pardoll DM, Itaya T, et al. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an immune response. Cell 1990, 60:397-403
84. Zitvogel L, Tahara H, Robbins PD, et al. Cancer immunotherapy of established tumors with IL-12: effective delivery by genetically engineered fibroblasts. J Immunol 1995;155:1393-1403
85. Nestle FO, Alijagic S, Gilliet M et al. Vaccination of melanoma patients with peptide- or tumor lysate pulsed dendritic cells. Nat Med, 1998;4:328-332
86. Mukherji B, Chakraborty NG, Yamasaki S et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma immunization with synthetic peptide-pulsed tutologous antigen presenting cells. Proc Natl Acad Sci USA, 1995;92:8078-8082
87. Hsu FJ, Benike C, Fagnoni F et al. Vaccination of patients with β -catenin lymphoma using autologous antigen-pulsed dendritic cells. Nat Med, 1996;2:52-58
88. Herrmann F. Cancer gene therapy:principles, problems, and perspectives. J Mol Med ,1995;73:157-63
89. Hodgson CP. The vector void in gene therapy: can viral vectors and transfection be combined to permit safe, efficacious, and targeted gene therapy? BioTechnology ,1995;13:222-5
90. Li QT, Kay MA, Finegold M et al. Assessment of recombinant adenoviral vectors for hepatic gene therapy. Hum Gene Ther,1993;4:403-9
91. Peplinski GR, Tsung K, Whitman ED et al. Construction and expression in tumor cells of a recombinant vaccinia virus encoding human interleukin-1 beta. Ann Surg Oncol, 1995;2:151-9
92. Hodge JW, Abrams S, Schlom J et al. Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res. 1994;54:5552-5
93. Huang JH, Getty RR, Chisari FV et al. Protein transfer of preformed MHC-peptide complexes sensitizes target cells to T cell cytolysis. Immunity, 1994;1:607-613
94. Coeshott C, Grey HM. Transfer of antigen-presenting capacity to la-negative cells upon fusion with la-bearing liposomes. J Immunol, 1985;134:1343-1348
95. Huang JH, Greenspan NS, Tykocinski ML. Alloantigenic recognition of artificial glycosylphosphatidylinositol-anchored HLA-A2.1. Mol Immunol, 1994;31:1017-1028
96. Guo YJ, Wu MC, Chen H et al. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science, 1994;263:518-20
97. Cormier JN, Salgaller ML, Provette T et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1. J Immunother, 1997;3:258
98. Salgaller ML, Marincola FM, Cornier JN et al. Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides. Cancer Res, 1996;56:4749-57
99. Cormier JN, Salgaller ML, Prevette T et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A. Cancer J Sci Am, 1997;3:37-44
100. Gilboa E. Immunotherapy of cancer with genetically modified tumor vaccines. Semin Oncol, 1996;23:101-7
101. .Parkhurse MR, Salgaller ML, Southwood S et al. Improved induction of melanoma reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0210 binding residues. J Immunol 1995; 157:2539-48
102. Rosenberg SA, Yang JC, Schwartzentruber DJ et al. Immunologic and therapeutic evaluation of a synthetic tumor-associated peptide vaccine for the treatment of patients with metastatic melanoma.Nat Med, 1998;4:321-327
103. Spooner RA, Deonarain MP, Epenetos AA et al. DNA vaccination ofr cancer treatment. Gene Ther 1995;2:173-80
104. Wang M, Bronte V, Chen PW et al. Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor associated atigen. J Immunol, 1995; 154:4685-92
105. Chen PW, Wang M, Bronte V et al. Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen. J Im muno 1996;156:224-31
106. Tsujimoto M, Kotani S, Okunaga T et al. Enhancement of humoral immune responses against viral by a non-pyrogenic 6-0-acyl- muramyldipeptide and synthetic low toxicity analogues of lipid a.Vaccine, 1989,7:39
107. Kleinerman ES, Jia SF, Griffin J et al. Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration.J Clin Oncol. 1992,10:1310-6
108. Kleinerman ES. Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide. Hematol Oncol Clin North Am 1995, 9:927-38
109. Alving CR. Liposomes as carriers of antigens and adjuvants. J Immunological Methods. 1991,140:1 -13
110. Gregoriadis G. Immunological adjuvants: a role for liposomes. Immunology Today, 1990,11:89
111. Morein B. The iscoms: an immunostimulating system.Immunology Letters, 1990, 25:281
112. Allison AC, Byars NE. Immunological adjuvant: desirable properties and side-effects. Molecular Immunology. 1991, 28:279-84
113. Takayama K, Olsen M, Datta P et al. Adjuvant activity of non-ionic block copolymers. Vaccine, 1991, 9:255-65
114. Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science 1990,248:705-11
115. Ostrand-Rosenberg S, Pulaski BA, Clements VK et al. Cell-based vaccines for the stimulation of immunity to metastatic cancers. Immunological Riviews 1999, 170:101-114
116. Pulaski B, Ostrand-Rosenberg S. MHC class II and B7.1 immunotherapeutic cell-based vaccine reduces spontaneous mammary carcinoma metastases without affecting primary tumor growth. Cancer Res 1998;58:1486-93
117. Lednicky JA, Stewart AR, Jenkins JJ et al. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int J Cancer, 1997;72: 791-800
118. Macedo MF; Velders MP; Nieland JD et al. Cellular immunity and immunotherapy against deoxyribonucleic acid virus-induced tumors. Monaldi Arch Chest Dis, 1998; 53: 211-8
119. Olafsen T, Bruland OS, Zalutsky MR et al. Abundant tyrosine residues in the antigen binding site in anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Application to radiolabeling. Acta Oncol, 1996; 35: 297-301
120. Hjelstuen MH; Rasch Halvorsen K; Bruland O et al. Uptake,penetration, and binding of monoclonal antibodies with increasing affinity in human osteosarcoma multicell spheroids. Anticancer Res, 1998; 18: 3153-61
121. Olafsen T; Munthe Lund CK; Bruland OS et al. Complement-mediated lysis of cultured osteosarcoma cell lines using chimeric mouse/human TP-1 IgG1 and IgG3 antibodies. Cancer Immunol Immunother, 1999; 48: 411-8
122. Larsen RH; Bruland OS; Hoff P et al. Inactivation of human osteosarcoma cells in vitro by 211At-TP-3 monoclonal antibody: comparison with astatine-211-labeled bovine serum albumin, free astatine-211 and external-beam X rays. Radiat Res, 1994; 139:178-84
123. Larsen RH; Bruland OS; Hoff P et al. Analysis of the therapeutic gain in the treatment of human osteosarcoma microcolonies in vitro with 211At-labelled monoclonal antibody. Br J Cancer, 1994;69: 1000-5
124. Sudo T; Kuramoto T; Komiya S et al. Expression of MAGE genes in osteosarcoma. J Orthop Res, 1997; 15: 128-32
125. Hayakawa M, Kauaguchi S, Ishii S et al. B7-1 transfected tumor vaccine counteracts chemotherapy-induced immunosuppression and prolongs the survival of rat bearing highly metastatic osteosarcoma cells. Int J Cancer 1997;71:1091-1102
126. Visonneau S; Cesano A; Jeglum KA et al. Adjuvant treatment of canine osteosarcoma with the human cytotoxic T-cell line TALL-104. Clin Cancer Res, 1999; 5: 1868-75
127. Killion JJ; Fidler IJ. Systemic targeting of liposome-encapsulated immunomodulators to macrophages for treatment of cancer metastasis. Immunomethods, 1994; 4: 273-9
128. Thacker JD; Dedhar S; Hogge DE. The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo. Int J Cancer, 1994; 56: 236-43
129. Cmalic S; Hakansson I; Boquist L et al. A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice. Clin Exp Metastasis, 1997 ; 15: 164-72
130. Tsang KY; Pan JF; Fudenberg HH. An animal model for evaluation of antigen-specific dialyzable leukocyte extracts therapy of osteosarcoma. Clin Immunol Immunopathol, 1987;42: 360-9
131. Shirakawa T; Ko SC; Gardner TA et al. In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy. Cancer Gene Ther, 1998;5:274-80
132. Shoieb AM; Hahn KA; Barnhill MA. An in vivo/in vitro experimental model system for the study of human osteosarcoma: canine osteosarcoma cells (COS31) which retain osteoblastic and metastatic properties in nude mice. In Vivo, 1998;12: 463-72
133. Withrow SJ; Powers BE; Straw RC et al. Comparative aspects of osteosarcoma. Dog versus man. Clin Orthop, 1991;Sep: 159-68
134. Kamel HM; Merry S; Toner PG. Mechanism of actinomycin D-induced resistance in Ridgway osteogenic sarcoma: an ultrastructural study. J Submicrosc Cytol Pathol, 1988; 20: 225-35
135. Manusama ER; Stavast J; Durante NM et al. Isolated limb perfusion with TNF alpha and melphalan in a rat osteosarcoma model: a new anti-tumour approach. Eur J Surg Oncol, 1996; 22:152-7
136. Witzel JG; Prescher A; Weisser H. Experimental animal model for the evaluation of chemotherapeutical effects on osteosarcoma. Chemotherapy, 1992; 38: 251-60
137. Witzel JG; Bohndorf K; Prescher A et al. Osteosarcoma of the nude rat. A model for experimental magnetic resonance imaging studies of bone tumors. Invest Radiol, 1992; 27: 205-10
138. Witzel JG; Prescher A. An experimental osteosarcoma of the athymic nude rat. Invasion Metastasis, 1991; 11: 110-5
139. Bell RS; Roth YF; Gebhardt MC. Timing of chemotherapy and surgery in a murine osteosarcoma model. Cancer Res, 1988; 48:5533-8
140. Mori S, Ueda T, Kuratsu S et al. Suppression of pulmonary metastasis by angiogenesis inhibitor TNP-470 in murine osteosarcoma. Int. J. Cancer. 1995,61:148-152
141. Satomura T. Biological characterization of a hamster osteosarcoma Os 515--development of lung metastasis.Nippon-Seikeigeka-Gakkai-Zasshi. 1985; 59: 773-84
142. Sekiguchi M; Satomura T; Saegusa M et al. An experimental transplantable osteosarcoma with spontaneous pulmonary metastasis in hamsters. Invasion Metastasis,1993;13:119-123
143. Hiruma T. Rabbit osteosarcoma induced by hydroxypropylcellulose mixed beryllium oxide pellet--comparison between implantations into bone marrow cavity and into fracture callus of the femur.Nippon Seikeigeka Gakkai Zasshi, 1991; 65:775-86
144. Pelfrene AF.A search for a suitable animal model for bone tumors: a review. Drug Chem Toxicol, 1985; 8: 83-99
145. Rosenberg SA. The immunotherapy of solid cancers based on cloning the genes encoding tumor-rejection antigens. Annu Rev Med 1996;47:481-91
146. Boon T, Cerottini JC, Vanden Eynde B et al. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 1994;12:337-65
147．郝新保，张利朝，殷樱 等．MTT比色法测定细胞生长曲线．第四军医大学学报，1997；18：390-391
148. Maeda K, Sato T, Azuma M et al. Characterization of rat CD80 and CD86 by molecular cloning and mAb. International Immunology, 1997;9:993-1000
149. Martin TJ, Ingleton PM, Underwood JCE et al. Paxathyroid hormone-responsive adenylate cyclase in induced transplantable osteogenic rat sarcoma. Nature, 1976;260:436-438
150．章卫平，曹雪涛，黄欣等．基因修饰的树突状细胞融合后的瘤苗抗肿瘤免疫应答的实验研究．中华医学杂志，1997；77：39-42
151．张殿忠，范清宇，马保安等．人骨肉瘤细胞系OS-9901的建立及其生物学特性．第四军医大学学报，1999；20：1048-1050
152．张伟滨，沈才伟，蔡体栋 等．HLA表现型与骨肉瘤相关性研究．中华骨科杂志，1997；17：419-21．
2. Rosenberg SA. The immunotherapy and gene therapy of cancer. J Clin Oncol 1992;10:180-199
3. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes Science 1986;233:1318-1321
4. Kast WM, Offringa R, Peters PJ et al. Eradication of adenovirus E1-induced tumors by E1A specific cytotoxic T lymphocytes. Cell,1989;59:603-614
5. Greenbeerg PD. Adoptive T cell therapy of tumors: mechanisms operative in the recognition and elimination of tumor cells. Adv Immunol 1991;49:281-355
6. Disis ML, Cheever MA. HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Adv Cancer Res 1992;21:343-71
7. Apostolopoulos V, McKenzie IF, Pietersz GA et al. Breast cancer immunotherapy : current status and future prospects. Immunol Cell Biol 1996;74:457-64
8. Van den Eynde B, Van der Bruggen P. T cell-defined tumor antigens. Curr Opin Immunol 1997;9:684-693
9. Muul LM, Spiess PJ, Director EP et al. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol, 1987;138:989-95
10.Itoh K, Platsoucas CD, Balch CM. Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas: activation by interleukin 2 and autologous tumor cells,and involvement of the T cell receptor. J Exp Med 1988;168:1419-41
11. Belldegrun A, Kasid A, Uppenkamp M, et al. Human tumor infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. J Immunol,1989;142:4520-6
12. O'Neil BH, Kawakami Y, Restifo NP et al. Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA. J Immunol,1993;151:1410-18
13. Peoples GE, Goedegebuure PS, Andrews JV et al. HLA-A2 presents shared tumor-associated antigens derived from endogenous proteins in ovarian cancer. J Immunol 1993;151:5481-91
14. Ioannides CG, PlatsoucasCD, Rashed S, et al. Tumor cytolysis by lymphocytes infiltrating ovarian malignant ascites. Cancer Res 1991;51:4257-65
15. Hom SS, Rosenberg SA, Topalian SL. Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas: analysis by cytokine secretion. Cancer Immunol Immunother 1993;36:1-8
16. Schwartzentruber DJ, Solomon D, RosenbergSA, et al.Characterization of lymphocytes infiltrating human breast cancer:specific immune reactivity detected by measuring cytokine secretion. J Immunother 1992;12:1-12
17. Schendel DJ, Gansbacher B, Oberneder R, et al. Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. 1. HLA-A2-restricted recognition ofautologous and allogeneic tumor lines. J Immunol 1993;151:4209-20
18. Kawakami Y, Eliyahu S, Delgado CH, et al. Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection. Proc Natl Acad Sci USA 1994;91:6458-62
19. Kawakami Y, Elyyahu S, Delgado CH, et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc Natl Acad Sci USA 1994;91:3515-9
20. Robbins PF, El-Gamil M, Kawakami Y, et al.Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy Cancer Res 1994;54:3124-6
21. Wang RF, Robbin PF, Kawakami Y, et al. Identification of a gene encoding a melanoma tumor antigen recognized by HLA-A31- restricted tumor infiltrating lymphocytes. J Exp Med 1995;181:799-804
22. Coulie P, Brichard V, Van Pel A, et al. A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 1995;190:1-4
23. Brichard V, Van Pel A, Wolfel T et al. The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-H2 melanomas. J Exp Med, 1993; 178:489-495
24. Bakker AB, Schreurs MW, de Boer AJ et al. Melanocyte lineage-specific antigen gp100 is recognized by melanocyte-derived tumor-infiltrating lymphocytes. J Exp Med, 1994; 179:1005-1009
25. Wang RF, Appella E, Kawakami Y, et al. Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.J Exp Med 1996;184:2207-2216
26. Van der Bruggen P, Traversari C, Chomez P et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science, 1991;254:1643-47
27. Van der Bruggen P, Bastin J, Gajewski T et al. A peptide encoded by human gene GAGE-3 and presented by HLA-A2 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE-3. Eur J Immunol, 1994;24:3038-3043
28. Herman J, Van der Bruggen P, Luescher IF et al. A peptide encoded by the human MAGE3 gene and presented by HLA-B44 induces cytolytic T lymphocytes that recognize tumor cells expressing MAGE3. Immunogenetics, 1996;43:377-383
29. Boel P, Wildmann C, Sensi ML et al. BAGE: a new gene encoding an antigen recognized on human melanomas by cytolytic T lymphocytes. Immunity, 1995;2:167-175
30. Van Den Eynde B, Peeters 0, De Backer O, et al. A new family of genes coding for an antigen recognized by autologous cytolytic T lymphocytes on a human melanoma. J Exp Med 1995;182:689-698
31. Chen YT, Scanlan MJ, Sahin U et al. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA, 1997;94:1914-1918
32. Jager E, Chen YT, Drijfhout JW et al. Simultaneous humoral and cellular immune response against cancer-testis antigen NY-ESO-1: definition of human histocompatibility leukocyte antigen(HLA)-A2-binding peptide epitopes. J Exp Med, 1998;187:265-270
33. Wang RF, Johnston SL, Zeng G et al. A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames. J Immunol,1998;161:3596-3606
34. Gaugler B, Brouwenstijn N, Vantomme V et al. A new gene coding for an antigen recognized by autologous cytolytic T lymphocytes on a human renal carcinoma. Immunogenetics,1996;44:323-330
35. Ioannides CG, Fisk B, Pollack MS et al. Cytotoxic T-cell clones isolated from ovarian tumour infiltrating lymphocytes recognize common determinants on nonovarian tumour clones. Scand j Immunol, 1993;37:413-424
36. Yoshino I, Peoples GE, Geoedegebauure PS et al. Association of HER2/neu expression with sensitivity to tumor-specific CTL in human ovarian cancer. J Immunol, 1994;152:2393-2400
37. Disis ML, Calenoff E, McLaughlin G et al. Existent T cell and antibody immunity to HER-2/neu protein in patients with brease cancer. Cancer Res, 1994;54:16-20
38. Peoples GE, Goedegebuure PS, Smith R et al. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci USA,1995;92:432-436
39. Linehan DC, Goedegebuure PS, peoples GE et al. Tumor-specific and HLA-A2-restricted cytolysis by tumor-associated lymphocytes in human metastatic breast cancer. J Immunol,1995; 155:4486-4491
40. Ioannides CG, Fisk B, Jerome KR et al. Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol, 1993;151:3693-3703
41. Magarian-Blander J, Domenech N, Finn OJ. Specific and effective T-cell recognition of cells transfected with a truncated human mucin cDNA. Ann NY Acad Sci 1993;690:231-243
42. Finn OJ, Jerome KR, Henderson RA et al. MUC-1 epithelial tumor mucin-based immunity and cancer vaccines. Immunol Rev,1995;145:61-89
43. Apostolopoulos V, Karanikas V, Haurum JS et al. Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J Immunol 1997;159:5211-5218
44. Coulie PG, Lehmann F, Lethe B et al. A mutated intron sequence codes for an antigenic peptide recognized by cytolytic T lymphocytes on a human melanoma. Proc natl Acad Sci USA,1995;92:7976-7980
45. Wolfel T, Hauer M, Schneider J et al. A p16-INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science, 1995;269:1281-1284
46. Mandruzzato S, Brasseur F, Andry G et al. A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma. J Exp Med, 1997;186:785-793
47. Robbins PF, E1-Gamil M, Li YF et al. A mutated β -catenin gene encodes a melanoma-spicific antigen recognized by tumor infiltrating lymphocytes. J Exp Med, 1996; 183:1185-1192
48. Kawanishi J, Kato J, Sasaki K et al. Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the β -catenin gene in a human cancer cell line, HSC-39. Mol Cell Biol, 1995;15:1175-1181
49. Korinek V, Barker N, Morin PJ et al. Constitutive transcriptional activation by a β -catenin-Tcf complex in APC-/- colon carcinoma. Science, 1997;275:1784-1787
50. Morin PJ, Sparks AB, Korinek V et al. Activation of β -catenin-Tcf signaling in colon cancer by mutations in betacatenin or APC.Science, 1997;275:1787-1790
51. Rubinfeld B, Robbins P, E1-Gamil M, et al. Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997;275:1790-1792
52. Ostrand-Rosenberg S. Tumor immunotherapy: the tumor cell as an antigen-presenting cell. Curr Opin Immunol 1994;6:722-727
53. Pardoll DM, Topalian S. The role of CD4+ T cell responses in antitumor immunity. Curr Opin Immunol 1998;10:588-594
54. Toes RE, Ossendorp F, Offringa R et al. CD4+ T cells and their role in antitumor immune responses. J Exp Med, 1999;189:753-756
55. Greenberg PD, Cheever MA, Fefer A. Eradication of disseminated murine leukemia by chemoimmunotherapy with cyclophosphamide and adoptively transferred immune syngeneic Lyt-1+2- lymphocytes. J Exp Med 1981 ;154:952-963
56. Schild HJ, Kyewski B, Von Hoegen P et al. CD4+ helper T cells are required for resistance to highly metastatic murine tumor. Eur j Immunol 1987;17:1863-1866
57. Romerdahl CA, Kripke ML. Role of helper T-lymphocytes in rejection of UV-induced murine skin cancers. Cancer Res 1988;48:2325-2328
58. Hung K, Hayashi R, Lafond-Walker A et al. The central role of CD4+ T cells in the antitumor immune response. J Exp Med 1998;188:2357-2368
59. Frasca L, Piazza C, Piccolella E. CD4+ T cells orchestrate both amplification and deletion of CD8+ T cells. Crit Rev Immunol 1998;18:569-594
60. Topalian SL, Rivoltini L, Mancini M et al. Human CD4+ T cells specifically recognize a shared melanoma-associated antigen encoded by the tyrosinase gene. Proc Natl Acad Sci USA,1994;91:9461-9465
61. Topalian SL, Gonzales MI, Parkhurst M et al. Melanoma-specific CD4+ T cell recognize nonmutated HLA-DR- restricted tyrosinase epitopes. J Exp Med, 1996; 183:1965-1971
62. Haider T, Pawelec G, Kirkin AF et al. Isolation of novel HLA-DR restricted potential tumor-associated antigens from the melanoma cell line FM3. Cancer Res, 1997;57:3238-3244
63. Chaux P, Vantomme V, Stroobant V et al. Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4+ T lymphocytes. J Exp Med, 1999; 189:767-778
64. Manici S, Sturniolo T, Imro MA et al. Melanoma cells present a MAGE-3 epitope to CD4+ cytotoxic T cells in association with histocompatibility leukocyte antigen DR11. J Exp Med,1999;189:871-876
65. Pieper R, Christian RE, Genzales MI et al. Biochemical identification of a mutated human melanoma antigen recognized by CD4+ T cells. J Exp Med, 1999; 189:757-766
66. Wang RF, Wang X, Atwood AC et al. Cloning genes encoding MHC class II-restricted antigens: mutated CDC27 as a tumour antigen. Science, 1999;284:1351-1354
67. Gareia Plata D, Mozos E, Sierra MA et al. HLA expression in basal cell carcinomas. Invasion Metastasis, 1991;11:166
68. Nouri AM, dos Santos AV, Crosby 0 et al. Correlation between class I antigen expression and the ability to generate tumour infiltrating lymphocytes from bladder tumour biopsies. Br j Cancer, 1991;64:996
69. Pardoll DM. Cancer vaccines. Immunol Today, 1993;14:310-316
70. Chamberlain RS, Carroll MW, Bronte V et al. Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines. Cance Res 1996;56:2832-6
71. McArthur JG, Raulet DH. CD28-induced costimulation of T helper type 2 cells mediated by induction responsiveness to interleukin 4. J Exp Med, 1993; 178:1645-53
72. Ramarathinam L, Castle M, Wu Y et al. T cell costimulation by B7/BBI induces CD8 T cell-dependent tumor rejection: an importment role of B7/BBI in the induction, recruitment, and effector function of antitumor T cells. J Exp Med, 1994;179:1025-1114
73. Chen L, Ashe, Brudy WA. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell, 1992;71:1093-l 102
74. Townsend SE, Allison JP. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells.Science, 1993;259:368-370
75. Li Y, McGowan P, Hellstrom I et al. Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J Immunol, 1994;153:421-8
76. Fenton RT, Sznol M, Kuster DG et al. A phase I trial of B7-transfected of parental lethally irradiated allogeneic melanoma cell lines to induce cell-mediated immunity against tumor-associated antigen presented by HLA-A2 or HLA-A1 in patients with stage IV melanoma. Human Gene Therapy, 1995;6:87-106
77. Pardoll D. Paracrine cytokine adjuvants in cancer immunotherapy.Annu Rev Immunol 1995;13:399-415
78. Golumbek PT, Lazenby AJ, Levitsky HI et al. Treatment of established renal cancer by tumor cell engineered to secrete interleukin-4. Science, 1991;254:713-716
79. Restifo NP, Spiese PJ, Karp SE et al. A nonimmunogenic sarcoma transducted with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability. J Exp Med, 1992:175:1423-1431
80. Colombo MP, Modesti A, Parmiani G et al. Local cytokine availability elicits tumor rejection and systemic immunity through granulocyte-T- lymphocyte cross-talk. Cancer Res, 1992;52:4853-4857
81. Hock H, Dorsch M, Diamantstein T et al. Interleukin T induces CD4+ T cell-dependent tumor rejection. J Exp Med,1991;174:1291-1298
82. Colombo M, Forni G . Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 1994;15:48-51
83. Fearon ER, Pardoll DM, Itaya T, et al. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an immune response. Cell 1990, 60:397-403
84. Zitvogel L, Tahara H, Robbins PD, et al. Cancer immunotherapy of established tumors with IL-12: effective delivery by genetically engineered fibroblasts. J Immunol 1995;155:1393-1403
85. Nestle FO, Alijagic S, Gilliet M et al. Vaccination of melanoma patients with peptide- or tumor lysate pulsed dendritic cells. Nat Med, 1998;4:328-332
86. Mukherji B, Chakraborty NG, Yamasaki S et al. Induction of antigen-specific cytolytic T cells in situ in human melanoma immunization with synthetic peptide-pulsed tutologous antigen presenting cells. Proc Natl Acad Sci USA, 1995;92:8078-8082
87. Hsu FJ, Benike C, Fagnoni F et al. Vaccination of patients with β -catenin lymphoma using autologous antigen-pulsed dendritic cells. Nat Med, 1996;2:52-58
88. Herrmann F. Cancer gene therapy:principles, problems, and perspectives. J Mol Med ,1995;73:157-63
89. Hodgson CP. The vector void in gene therapy: can viral vectors and transfection be combined to permit safe, efficacious, and targeted gene therapy? BioTechnology ,1995;13:222-5
90. Li QT, Kay MA, Finegold M et al. Assessment of recombinant adenoviral vectors for hepatic gene therapy. Hum Gene Ther,1993;4:403-9
91. Peplinski GR, Tsung K, Whitman ED et al. Construction and expression in tumor cells of a recombinant vaccinia virus encoding human interleukin-1 beta. Ann Surg Oncol, 1995;2:151-9
92. Hodge JW, Abrams S, Schlom J et al. Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res. 1994;54:5552-5
93. Huang JH, Getty RR, Chisari FV et al. Protein transfer of preformed MHC-peptide complexes sensitizes target cells to T cell cytolysis. Immunity, 1994;1:607-613
94. Coeshott C, Grey HM. Transfer of antigen-presenting capacity to la-negative cells upon fusion with la-bearing liposomes. J Immunol, 1985;134:1343-1348
95. Huang JH, Greenspan NS, Tykocinski ML. Alloantigenic recognition of artificial glycosylphosphatidylinositol-anchored HLA-A2.1. Mol Immunol, 1994;31:1017-1028
96. Guo YJ, Wu MC, Chen H et al. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science, 1994;263:518-20
97. Cormier JN, Salgaller ML, Provette T et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1. J Immunother, 1997;3:258
98. Salgaller ML, Marincola FM, Cornier JN et al. Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides. Cancer Res, 1996;56:4749-57
99. Cormier JN, Salgaller ML, Prevette T et al. Enhancement of cellular immunity in melanoma patients immunized with a peptide from MART-1/Melan A. Cancer J Sci Am, 1997;3:37-44
100. Gilboa E. Immunotherapy of cancer with genetically modified tumor vaccines. Semin Oncol, 1996;23:101-7
101. .Parkhurse MR, Salgaller ML, Southwood S et al. Improved induction of melanoma reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0210 binding residues. J Immunol 1995; 157:2539-48
102. Rosenberg SA, Yang JC, Schwartzentruber DJ et al. Immunologic and therapeutic evaluation of a synthetic tumor-associated peptide vaccine for the treatment of patients with metastatic melanoma.Nat Med, 1998;4:321-327
103. Spooner RA, Deonarain MP, Epenetos AA et al. DNA vaccination ofr cancer treatment. Gene Ther 1995;2:173-80
104. Wang M, Bronte V, Chen PW et al. Active immunotherapy of cancer with a nonreplicating recombinant fowlpox virus encoding a model tumor associated atigen. J Immunol, 1995; 154:4685-92
105. Chen PW, Wang M, Bronte V et al. Therapeutic antitumor response after immunization with a recombinant adenovirus encoding a model tumor-associated antigen. J Im muno 1996;156:224-31
106. Tsujimoto M, Kotani S, Okunaga T et al. Enhancement of humoral immune responses against viral by a non-pyrogenic 6-0-acyl- muramyldipeptide and synthetic low toxicity analogues of lipid a.Vaccine, 1989,7:39
107. Kleinerman ES, Jia SF, Griffin J et al. Phase II study of liposomal muramyl tripeptide in osteosarcoma: the cytokine cascade and monocyte activation following administration.J Clin Oncol. 1992,10:1310-6
108. Kleinerman ES. Biologic therapy for osteosarcoma using liposome-encapsulated muramyl tripeptide. Hematol Oncol Clin North Am 1995, 9:927-38
109. Alving CR. Liposomes as carriers of antigens and adjuvants. J Immunological Methods. 1991,140:1 -13
110. Gregoriadis G. Immunological adjuvants: a role for liposomes. Immunology Today, 1990,11:89
111. Morein B. The iscoms: an immunostimulating system.Immunology Letters, 1990, 25:281
112. Allison AC, Byars NE. Immunological adjuvant: desirable properties and side-effects. Molecular Immunology. 1991, 28:279-84
113. Takayama K, Olsen M, Datta P et al. Adjuvant activity of non-ionic block copolymers. Vaccine, 1991, 9:255-65
114. Marrack P, Kappler J. The staphylococcal enterotoxins and their relatives. Science 1990,248:705-11
115. Ostrand-Rosenberg S, Pulaski BA, Clements VK et al. Cell-based vaccines for the stimulation of immunity to metastatic cancers. Immunological Riviews 1999, 170:101-114
116. Pulaski B, Ostrand-Rosenberg S. MHC class II and B7.1 immunotherapeutic cell-based vaccine reduces spontaneous mammary carcinoma metastases without affecting primary tumor growth. Cancer Res 1998;58:1486-93
117. Lednicky JA, Stewart AR, Jenkins JJ et al. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int J Cancer, 1997;72: 791-800
118. Macedo MF; Velders MP; Nieland JD et al. Cellular immunity and immunotherapy against deoxyribonucleic acid virus-induced tumors. Monaldi Arch Chest Dis, 1998; 53: 211-8
119. Olafsen T, Bruland OS, Zalutsky MR et al. Abundant tyrosine residues in the antigen binding site in anti-osteosarcoma monoclonal antibodies TP-1 and TP-3: Application to radiolabeling. Acta Oncol, 1996; 35: 297-301
120. Hjelstuen MH; Rasch Halvorsen K; Bruland O et al. Uptake,penetration, and binding of monoclonal antibodies with increasing affinity in human osteosarcoma multicell spheroids. Anticancer Res, 1998; 18: 3153-61
121. Olafsen T; Munthe Lund CK; Bruland OS et al. Complement-mediated lysis of cultured osteosarcoma cell lines using chimeric mouse/human TP-1 IgG1 and IgG3 antibodies. Cancer Immunol Immunother, 1999; 48: 411-8
122. Larsen RH; Bruland OS; Hoff P et al. Inactivation of human osteosarcoma cells in vitro by 211At-TP-3 monoclonal antibody: comparison with astatine-211-labeled bovine serum albumin, free astatine-211 and external-beam X rays. Radiat Res, 1994; 139:178-84
123. Larsen RH; Bruland OS; Hoff P et al. Analysis of the therapeutic gain in the treatment of human osteosarcoma microcolonies in vitro with 211At-labelled monoclonal antibody. Br J Cancer, 1994;69: 1000-5
124. Sudo T; Kuramoto T; Komiya S et al. Expression of MAGE genes in osteosarcoma. J Orthop Res, 1997; 15: 128-32
125. Hayakawa M, Kauaguchi S, Ishii S et al. B7-1 transfected tumor vaccine counteracts chemotherapy-induced immunosuppression and prolongs the survival of rat bearing highly metastatic osteosarcoma cells. Int J Cancer 1997;71:1091-1102
126. Visonneau S; Cesano A; Jeglum KA et al. Adjuvant treatment of canine osteosarcoma with the human cytotoxic T-cell line TALL-104. Clin Cancer Res, 1999; 5: 1868-75
127. Killion JJ; Fidler IJ. Systemic targeting of liposome-encapsulated immunomodulators to macrophages for treatment of cancer metastasis. Immunomethods, 1994; 4: 273-9
128. Thacker JD; Dedhar S; Hogge DE. The effect of GM-CSF and G-CSF on the growth of human osteosarcoma cells in vitro and in vivo. Int J Cancer, 1994; 56: 236-43
129. Cmalic S; Hakansson I; Boquist L et al. A novel spontaneous metastasis model of human osteosarcoma developed using orthotopic transplantation of intact tumor tissue into tibia of nude mice. Clin Exp Metastasis, 1997 ; 15: 164-72
130. Tsang KY; Pan JF; Fudenberg HH. An animal model for evaluation of antigen-specific dialyzable leukocyte extracts therapy of osteosarcoma. Clin Immunol Immunopathol, 1987;42: 360-9
131. Shirakawa T; Ko SC; Gardner TA et al. In vivo suppression of osteosarcoma pulmonary metastasis with intravenous osteocalcin promoter-based toxic gene therapy. Cancer Gene Ther, 1998;5:274-80
132. Shoieb AM; Hahn KA; Barnhill MA. An in vivo/in vitro experimental model system for the study of human osteosarcoma: canine osteosarcoma cells (COS31) which retain osteoblastic and metastatic properties in nude mice. In Vivo, 1998;12: 463-72
133. Withrow SJ; Powers BE; Straw RC et al. Comparative aspects of osteosarcoma. Dog versus man. Clin Orthop, 1991;Sep: 159-68
134. Kamel HM; Merry S; Toner PG. Mechanism of actinomycin D-induced resistance in Ridgway osteogenic sarcoma: an ultrastructural study. J Submicrosc Cytol Pathol, 1988; 20: 225-35
135. Manusama ER; Stavast J; Durante NM et al. Isolated limb perfusion with TNF alpha and melphalan in a rat osteosarcoma model: a new anti-tumour approach. Eur J Surg Oncol, 1996; 22:152-7
136. Witzel JG; Prescher A; Weisser H. Experimental animal model for the evaluation of chemotherapeutical effects on osteosarcoma. Chemotherapy, 1992; 38: 251-60
137. Witzel JG; Bohndorf K; Prescher A et al. Osteosarcoma of the nude rat. A model for experimental magnetic resonance imaging studies of bone tumors. Invest Radiol, 1992; 27: 205-10
138. Witzel JG; Prescher A. An experimental osteosarcoma of the athymic nude rat. Invasion Metastasis, 1991; 11: 110-5
139. Bell RS; Roth YF; Gebhardt MC. Timing of chemotherapy and surgery in a murine osteosarcoma model. Cancer Res, 1988; 48:5533-8
140. Mori S, Ueda T, Kuratsu S et al. Suppression of pulmonary metastasis by angiogenesis inhibitor TNP-470 in murine osteosarcoma. Int. J. Cancer. 1995,61:148-152
141. Satomura T. Biological characterization of a hamster osteosarcoma Os 515--development of lung metastasis.Nippon-Seikeigeka-Gakkai-Zasshi. 1985; 59: 773-84
142. Sekiguchi M; Satomura T; Saegusa M et al. An experimental transplantable osteosarcoma with spontaneous pulmonary metastasis in hamsters. Invasion Metastasis,1993;13:119-123
143. Hiruma T. Rabbit osteosarcoma induced by hydroxypropylcellulose mixed beryllium oxide pellet--comparison between implantations into bone marrow cavity and into fracture callus of the femur.Nippon Seikeigeka Gakkai Zasshi, 1991; 65:775-86
144. Pelfrene AF.A search for a suitable animal model for bone tumors: a review. Drug Chem Toxicol, 1985; 8: 83-99
145. Rosenberg SA. The immunotherapy of solid cancers based on cloning the genes encoding tumor-rejection antigens. Annu Rev Med 1996;47:481-91
146. Boon T, Cerottini JC, Vanden Eynde B et al. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol 1994;12:337-65
147．郝新保，张利朝，殷樱 等．MTT比色法测定细胞生长曲线．第四军医大学学报，1997；18：390-391
148. Maeda K, Sato T, Azuma M et al. Characterization of rat CD80 and CD86 by molecular cloning and mAb. International Immunology, 1997;9:993-1000
149. Martin TJ, Ingleton PM, Underwood JCE et al. Paxathyroid hormone-responsive adenylate cyclase in induced transplantable osteogenic rat sarcoma. Nature, 1976;260:436-438
150．章卫平，曹雪涛，黄欣等．基因修饰的树突状细胞融合后的瘤苗抗肿瘤免疫应答的实验研究．中华医学杂志，1997；77：39-42
151．张殿忠，范清宇，马保安等．人骨肉瘤细胞系OS-9901的建立及其生物学特性．第四军医大学学报，1999；20：1048-1050
152．张伟滨，沈才伟，蔡体栋 等．HLA表现型与骨肉瘤相关性研究．中华骨科杂志，1997；17：419-21．