单倍体相合细胞移植治疗小鼠H22实体瘤的实验研究
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摘要
免疫治疗是恶性肿瘤的重要治疗手段之一。由于在异基因造血干细胞移植(Allo-HSCT)中观察到移植物抗白血病(GVL)效应的存在,并发现移植后进行供者淋巴细胞输注(DLI)可以增加抗肿瘤效应,人们开始对这种现象进行研究。目前,异基因造血干细胞移植不仅是一种提高化疗剂量的载体,而且已被作为一种肿瘤免疫治疗的手段。但这种治疗手段具有较高的治疗风险和存在供者来源不足的问题,虽然非清髓造血干细胞移植(NST)的开展在一定程度上降低了治疗的风险,主要组织相容抗原复合物(MHC)不全相合移植的发展解决了供者来源不足的问题,但移植相关并发症和移植相关死亡率(TRM)仍是限制其实际应用的主要障碍。如何保留移植物抗肿瘤(GVT)效应而降低TRM、扩大异基因免疫治疗的实际(特别是在实体瘤方面)应用范围,是临床的一大课题。
在本研究中,我们通过动物实验,对单倍体相合细胞移植诱发GVT效应进行观察,并对如何减轻GVHD以及GVT的效应机制进行初步的探索。
第一部分:可供单倍体相合移植研究的实体瘤动物模型的建立。实验共进行三次,每次6只F1小鼠。方法:将BABL/C来源的H22肝癌细胞接种于BALB/C×C57BL/6杂交F1代小鼠皮下,通过观察接种H22细胞后F1小鼠肿瘤的形成、生长过程,测量肿瘤大小并计算肿瘤体积的变异系数,探索H22细胞在F1小鼠的成瘤性;以流式细胞仪检测H22细胞的MHC表型;对实体瘤组织进行病理学观察。结果:每只F1小鼠右腋皮下接种2×10~6个H22细胞5、6天后,肿瘤开始长出,成瘤率为100%,肿瘤生长速度尚均匀,接种第14天时,三次实验的肿瘤体积变异系数分别为23%、34%、27%,肿瘤无自发缓解,全部小鼠
In the last two decades, various immunological strategies have been assessed to stimulate antitumor immunity in cancer patients. In this field, there is a growing perception that the graft-versus-leukemia (GVL) reaction induced by allogeneic hematopoietic stem cell transplantation (HSCT) is the most potent form of cancer immunotherapy in current clinical use, and that the donor lymphocyte infusion (DLI) following HSCT induces effective graft-versus-tumor responses in patients with posttransplantation leukemic relapse. Allogeneic hematopoietic stem cell transplantation is currently being used as a therapy for hematological malignancies and some solid tumors. Nevertheless, its clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. Laying the foundation for the development of novel immunotherapeutic strategies, new concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. Yet the application of this approach is still limited due to the treatment-related complications, transplant-related mortality (TRM), and recurrent malignancy. In the near future the major challenge for investigators in this field will be how to maximize the GVT effect while avoid or minimize GVHD.
In this study, the effects of graft-versus-tumor (GVT) induced by the allogeneic
在本研究中,我们通过动物实验,对单倍体相合细胞移植诱发GVT效应进行观察,并对如何减轻GVHD以及GVT的效应机制进行初步的探索。
第一部分:可供单倍体相合移植研究的实体瘤动物模型的建立。实验共进行三次,每次6只F1小鼠。方法:将BABL/C来源的H22肝癌细胞接种于BALB/C×C57BL/6杂交F1代小鼠皮下,通过观察接种H22细胞后F1小鼠肿瘤的形成、生长过程,测量肿瘤大小并计算肿瘤体积的变异系数,探索H22细胞在F1小鼠的成瘤性;以流式细胞仪检测H22细胞的MHC表型;对实体瘤组织进行病理学观察。结果:每只F1小鼠右腋皮下接种2×10~6个H22细胞5、6天后,肿瘤开始长出,成瘤率为100%,肿瘤生长速度尚均匀,接种第14天时,三次实验的肿瘤体积变异系数分别为23%、34%、27%,肿瘤无自发缓解,全部小鼠
In the last two decades, various immunological strategies have been assessed to stimulate antitumor immunity in cancer patients. In this field, there is a growing perception that the graft-versus-leukemia (GVL) reaction induced by allogeneic hematopoietic stem cell transplantation (HSCT) is the most potent form of cancer immunotherapy in current clinical use, and that the donor lymphocyte infusion (DLI) following HSCT induces effective graft-versus-tumor responses in patients with posttransplantation leukemic relapse. Allogeneic hematopoietic stem cell transplantation is currently being used as a therapy for hematological malignancies and some solid tumors. Nevertheless, its clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. Laying the foundation for the development of novel immunotherapeutic strategies, new concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. Yet the application of this approach is still limited due to the treatment-related complications, transplant-related mortality (TRM), and recurrent malignancy. In the near future the major challenge for investigators in this field will be how to maximize the GVT effect while avoid or minimize GVHD.
In this study, the effects of graft-versus-tumor (GVT) induced by the allogeneic
引文
1. Long EO B D, Clark WP, et al. Killer cell inhibitory receptors: divercity, specificity, and function. Immunol Rev, 1997. 155: 135-144.
2. Lanier LL. NKcell receptors. Anna Rev Immunol, 1998. 16: 359-393.
3. Garrido F, Ruiz-Cabello F, Cabrera T, et al. Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today, 1997. 18(2): 89-95.
4. Ruiz-Cabello F G F. HLA and cancer: from research to clinlcal impact. Immunol Today, 1998. 19: 539-542.
5. Paul P, Rouas-Freiss N, Khalil-Daher I, et al. HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance. Proc Natl Acad Sci U S A, 1998. 95(8): 4510-4515.
6. Carosella E D, Dausset J, Rouas-Freiss N. Transplacental transmission of natural-killer-cell lymphoma. N Engl J Med, 1999. 341(25): 1937.
7. Storb R F, Lucarelli G, McSweeney P A, et al. Hematopoietic cell transplantation for benign hematological disorders and solid tumors. Hematology (Am Soc Hematol Educ Program), 2003: 372-397.
8. Porter D L, Connors J M, Van Deerlin V M, et al. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol, 1999. 17(4): 1234.
9. Collins R H Jr, Shpilberg O, Drobyski W R, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol, 1997. 15(2): 433-444.
10. Mapara M Y, Sykes M. Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol, 2004. 22(6): 1136-1151.
11. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science, 2002. 295(5562): 2097-2100.
12. Butcher B W, Collins R H, Jr. The graft-versus-lymphoma effect: clinical review and future opportunities. Bone Marrow Transplant, 2005. 36(1): 1-17.
13. Porter D L. The graft-versus-tumor potential of allogeneic cell therapy: an update on donor leukocyte infusions and nonmyeloablative allogeneic stem cell transplantation. J Hematother Stem Cell Res, 2001. 10(4): 465-480.
14. 韩伟,陆道培,黄晓军,等. HLA 配型不相合造血干细胞移植 GIAC 方案 100 例临床分析. 中华血液学杂志,2004. 25(8): 453-457.
15. 段连宁,郭坤元,褚建新,等. 小鼠红白血病在半相合型小鼠体内的生物特性. 中国实验血液学杂志,2002. 12(1): 108-114.
16. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood, 1998. 91(3): 756-763.
17. Gleichmann E, Gleichmann H, Wilke W. Autoimmunization and lymphomagenesis in parent to F1 combinations differing at the major histocompatibility complex: model for spontaneous disease caused by altered self-antigens? Transplant Rev, 1976. 31: 156-224.
18. Carayanniotis G, Halloran P F. Differential resistance to growth of a tumor expressing incompatible minor alloantigens reflects regulatory influences rather than differences in anti-minor-CTL-P frequencies. Cell Immunol, 1985. 91(1): 100-110.
19. Morecki S, Moshel Y, Gelfend Y, et al. Induction of graft vs. tumor effect in a murine model of mammary adenocarcinoma. Int J Cancer, 1997. 71(1): 59-63.
20. Morecki S, Yacovlev E, Diab A, et al. Allogeneic cell therapy for a murine mammary carcinoma. Cancer Res, 1998. 58(17): 3891-3895.
21. Weiss L, Reich S, Slavin S. Allogeneic cell therapy in murine B-cell leukemia (BCL1): 1. Alloimmune-mediated graft-versus-leukemia (GVL) effects induced by unmodified and in vitro rIL-2-activated bone marrow and lymphocytes from different lymphoidcompartments. Cytokines Cell Mol Ther, 1999. 5(3): 145-152.
22. Plytycz B, Seljelid R. Hybrid resistance to the ascites form of the murine sarcoma. Arch Immunol Ther Exp (Warsz), 1987. 35(6): 863-869.
23. Saitoh A, Yasaka N, Osada A, et al. Migration of Langerhans cells in an in vitro organ culture system: IL-6 and TNF-alpha are partially responsible for migration into the epidermis. J Dermatol Sci, 1999. 19(3): 166-174.
24. Pirozhkov A V, Dozmorov I M, Petrov R V. The growth of hemopoietic stem cells is inhibited by natural killers only in the nonsyngeneic microenvironment. Transplantation, 1994. 58(3): 345-349.
25. Shibata Y, Volkman A. Restoration of prostaglandin releasing macrophage populations in lethally irradiated mice with spleen cells from bone marrow-depleted donors. J Leukoc Biol, 1991. 49(4): 397-406.
26. Hui K M, Sim T, Foo T T, et al. Tumor rejection mediated by transfection with allogeneic class I histocompatibility gene. J Immunol, 1989. 143(11): 3835-3843.
27. Skorski T, Kawalec M. Induction of immune resistance against L1210 lymphatic leukemia in mice after chemoradiotherapy of the leukemia and reconstitution with bone marrow purged from the leukemia with mafosfamide. Exp Hematol, 1988. 16(9): 782-784.
28. Vanclee A, Lutgens L C, Oving E B, et al. Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model. Bone Marrow Transplant, 2005. 36(10): 907-915.
29. Rosenstein M, Eberlein T J, and Rosenberg S A, Adoptive immunotherapy of established syngeneic solid tumors: role of T lymphoid subpopulations. J Immunol, 1984. 132(4): 2117-2122.
30. Li J J, Zhang Y, Zhang M W, et al. [Establishment of nonmyeloablative allogeneic stem cell transplantation model in H-2 haploidentical mice and its related study.]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2004. 12(5): 655-660.
31. Kitajima T, Iwashiro M, Kuribayashi K, et al. The role of CD4+ and CD8+ cells in normal F1 hybrid host in the resistance to lethal graft-versus-host disease induction by transfer of parent spleen cells. Immunol Lett, 1994. 40(3): 207-210.
32. 王剑锋,凌茂英,初海鹰,等. 小鼠腹水型肝癌细胞系(H22 - Fo/ L)的建立及其生物学特性. 中华病理学杂志,1991. 20(1): 65.
33. Zhu B D, Yuan S J, Xu J M, et al. [The effect of IRESSA on H22 mouse hepatocellular carcinoma]. Zhonghua Yi Xue Za Zhi, 2004. 84(8): 684-686.
34. Zhai Y, Lu Z J. Effect of Thalidomide on Tumor Growth in Mouse Hepatoma H22 Mode. Chinese Journal of Cancer, 2003. 22(12): 1301-1306.
35. 李海燕,方肇勤,梁尚华. 小鼠移植性肝癌(H22)模型的研究及在中医药抗肿瘤中的应用. 中国中医基础医学杂志,2000. 6(1): 27-30.
36. LIU Junxu,LU Zhanjun,WANG Xiufang,et al. The Comparison in Cellulate Characteristics among Murine Hepatoma22 Cell Lines from Different Institutes. Chin J Lab Anim Sci, 2001. 11(1): 23-27.
37. 刘军须,吕占军,王秀芳,等. 不同单位小鼠肝癌 H22 瘤株蛋白质组成比较研究. 实验动物科学与管理,2001. 18(1): 11-12.
38. 刘军须,刘福英,王秀芳,等. 小鼠肝癌 H22 克隆细胞株 H2D8 与其原瘤株武汉H22 的基本特性比较研究. 实验动物科学与管理,2002. 19(3): 1-4.
39. LIU Junxu,LIU Fuying,CAI Yuehua,et al. The Comparison in Biological Characteristics among Murine Hepatoma 22 Cell Lines from Different Institutes. Acta Laboratorium Animalis Scicetia Sinica, 2002. 10(1): 43-46.
40. 黄承钰,曾令福,徐亚林,等. 小鼠实体型肝癌 H22 移植实验条件探讨. 临床与实验病理学杂志,1997. 13(2): 188-189.
41. 张学军,潘崚,王福旭,等. 雷公藤甲素治疗异基因骨髓移植后 aGVHD 的实验研究. 中国免疫学杂志,2005. 21(8): 612-616.
42. Morecki S, Yacovlev E, Gelfand Y, et al. Cell therapy with preimmunized effector cells mismatched for minor histocompatible antigens in the treatment of a murine mammarycarcinoma. J Immunother, 2001. 24(2): 114-121.
43. Morecki S, Yacovlev E, Gelfand Y, et al. Allogeneic versus syngeneic killer splenocytes as effector cells for the induction of graft-versus-tumor effect. Biol Blood Marrow Transplant, 2004. 10(1): 40-48.
44. Kummar S, Ishii A, Yang H, et al. Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-betaI. Biology of Blood and Marrow Transplantation, 2001. 7: 25-30.
45. 陈字,丁天凌,陈勤奋,等. 非清髓异基因骨髓移植小鼠模型的建立. 上海实验动物科学,2002. 24(2): 81-84.
46. Champlin R, Khouri I, Komblau S, et al. Reinventing bone marrow transplantation. Nonmyeloablative preparative regimens and induction of graft-vs-malignancy effect. Oncology (Williston Park), 1999. 13(5): 621-628; discussion 631, 635-628, 641.
47. Giralt S, Khouri I, and Champlin R, Non myeloablative "mini transplants". Cancer Treat Res, 1999. 101: 97-108.
48. Sandmaier B M, McSweeney P, Yu C, et al. Nonmyeloablative transplants: preclinical and clinical results. Semin Oncol, 2000. 27(2 Suppl 5): 78-81.
49. Peccatori J, Barkholt L, Demirer T, et al. Prognostic factors for survival in patients with advanced renal cell carcinoma undergoing nonmyeloablative allogeneic stem cell transplantation. Cancer, 2005. 104(10): 2099-2103.
50. Ballen K K, Becker P S, Emmons R V, et al. Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood, 2002. 100(2): 442-450.
51. Montefusco V. To the editor: Donor lymphocyte infusions as primary therapy for neoplasms. Karen Ballen, Peter Quesenberry. Response: Low-dose TBI for malignancy: cellular immune therapy.Correspondence. Blood, 2003. 101(1): 373-373.
52. Strair R K, Schaar D, Medina D, et al. Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma. J Clin Oncol,2003. 21(20): 3785-3791.
53. 韦大文,贾玉梅,李中正. 紫金散对 H22 小鼠肝癌实体瘤及腹水瘤抑瘤率的实验研究. 中国中药杂志,2005. 17(9): 1346-1348.
54. Emmenegger U, Man S, Shaked Y, et al. A comparative analysis of low-dose metronomic cyclophosphamide reveals absent or low-grade toxicity on tissues highly sensitive to the toxic effects of maximum tolerated dose regimens. Cancer Res, 2004. 64(11): 3994-4000.
55. Azoulay-Dupuis E, Bedos J P, Mohler J, et al. Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia. Antimicrob Agents Chemother, 2004. 48(4): 1105-1111.
56. Hermans I F, Chong T W, Palmowski M J, et al. Synergistic effect of metronomic dosing of cyclophosphamide combined with specific antitumor immunotherapy in a murine melanoma model. Cancer Res, 2003. 63(23): 8408-8413.
57. LI G-f, CAO J-g, ZHUANG Y-z. Synergetic Effect of Neferina on Cell Apoptosis Induced by Cyclophosphamide in Mice Lewis Lung Carcinoma. The Practical Journal of Cancer, 2005. 20(2): 135-137.
58. Henslee-Downey P J. Allogeneic transplantation across major HLA barriers. Best Pract Res Clin Haematol, 2001. 14(4): 741-754.
59. 张立成,郭坤元,董波,等. γ 射线照射单倍型供者淋巴细胞输注抗白血病作用的实验研究. 中华血液学杂志,2000. 21(2): 81-83.
60. 张立成,郭坤元,罗庆良,等. γ 射线照射预防供者淋巴细胞输注相关移植物抗宿主病的实验研究. 中华血液学杂志,1999. 20(9): 493-495.
61. 陈字,陈波斌,王钦红,等. γ 射线辐照抑制淋巴细胞增殖的剂量—效应关系研究. 中国临床医学,2003. 10(4): 540-541,544.
62. Guerriero A, Boyer M, Waller E, et al. γ irradiation activetes NF-κB in human T cells. The 39th Annual Meeting of Hematology, San Diego, 1997: 37.
63. Igietseme J U, Smith K, Simmons A, et al. Effect of gamma-irradiation on the effectorfunction of T lymphocytes in microbial control. Int J Radiat Biol, 1995. 67(5): 557-564.
64. Waller E, Redei I, Yeager A, et al. 7.5 Gy irradiation attenuates the graft-versus-host disease potential of allogenic lymphocytes while preserving antiluekemic activity in preclinical and clinical studies. Blood, 1997. 90(10 suppl 1): 547a.
65. 董陆佳. KIR 基因与异基因造血细胞移植. 中国实验血液学杂志,2004. 12(1): 108-114.
66. G.施蒂勒,P.瓦尔德编,朱立平,张伟译. 癌症免疫治疗[M].北京:化学工业出版社,2004(第一版): 166,279-289.
67. Renga M, Pedrazzoli P, and Siena S, Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors. Ann Oncol, 2003. 14(8): 1177-1184.
68. 郭亚军主编. 细胞生物学与肿瘤免疫学进展[M]. 北京:军事医学科学出版社, 2000(第一版): 30-39.
69. Matte C, Liu J, Cormier J, et al. Donor APCs are required for maximal GVHD but not for GVL. Nature Medicine, 2004. 10(9): 987-992.
70. Shlomchik W D. Antigen presentation in graft-vs-host disease. Experimental Hematology, 2003. 31(12): 1187-1197.
71. Guinan E, Gribben J, Boussiotis V, et al. Pivotal role of the B7:CD28 pathway in transplantation tolerance and tumor immunity. Blood, 1994. 84(10): 3361-3382.
72. Murphy W, Reynolds C, Tiberghien P, et al. Natural killer cells and bone marrow transplantation. Journal of the National Cancer Institute, 1993. 85(18): 1475-1482.
73. 田志刚,孙汭,William,等. NK 细胞用于肿瘤免疫治疗的研究进展. 中华微生物学和免疫学杂志,2001. 21(2): 239-240.
74. Groh V, Rhinehart R, Secrist H, et al. Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci U S A, 1999. 96(12): 6879-6884.
75. Vivier E, Tomasello E, Paul P. Lymphocyte activation via NKG2D: towards a newparadigm in immune recognition? Curr Opin Immunol, 2002. 14(3): 306-311.
76. Diefenbach A, Tomasello E, Lucas M, et al. Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol, 2002. 3(12): 1142-1149.
77. Ho E L, Carayannopoulos L N, Poursine-Laurent, et al. Costimulation of multiple NK cell activation receptors by NKG2D. J Immunol, 2002. 169(7): 3667-3675.
78. Zompi S, Hamerman J A, Ogasawara K, et al. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol, 2003. 4(6): 565-572.
79. Diefenbach A, Jensen E R, Jamieson A M, et al. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature, 2001. 413(6852): 165-171.
80. Liu Y X, Hu G L, Liu M, et al. [Study of the inhibiting effect of anti-NKG2D polyclonal antibody on cytotoxicities of NK and LAK cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2003. 19(3): 257-259.
81. McNerney M E, Lee K M, Zhou P, et al. Role of natural killer cell subsets in cardiac allograft rejection. Am J Transplant, 2006. 6(3): 505-513.
82. Ogasawara K, Benjamin J, Takaki R, et al. Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts. Nat Immunol, 2005. 6(9): 938-945.
83. Cerwenka A, Bakker A B, McClanahan T, et al. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity, 2000. 12(6): 721-727.
84. Radaev S, Kattah M, Zou Z, et al. Making sense of the diverse ligand recognition by NKG2D. J Immunol, 2002. 169(11): 6279-6285.
85. O'Callaghan C A, Cerwenka A, Willcox B E, et al. Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60. Immunity, 2001. 15(2): 201-211.
[1]Markus Y, Mapara, Megan Sykes. Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance. Journal of Clinical Oncology, 2004; 22: 1136-1151.
[2]Staveley O’Carroll K, Sotomayor E, Montgomery J, et al. Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acard Sci USA, 1998; 95: 1178-1183.
[3] Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood, 1998; 92(10): 3515-3520.
[4] Petersdorf EW, Longton GM, Anasetti C, et al. Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors. Blood, 1997; 89(5): 1818-1823.
[5] Shizuru JA, Jerabek L, Edwards CT et al. Transplantation of purified hematopoietic stem cells: requirements for overcoming the barriers of allogeneic engraftment. Biol Blood Marrow Transplant, 1996; 2: 3–14
[6] Shizuru JA, Weissman IL, Kernoff R et al. Purified hematopoietic stem cell grafts induce tolerance to alloantigens and can mediate positive and negative T cell selection. Proc Natl Acad Sci USA, 2000; 97: 9555–9560.
[7] Kyba M, Perlingeiro RC, Daley GQ. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell, 2002; 109: 29–37.
[8] Kaufman DS, Hanson ET, Lewis RL, et al. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci USA, 2001; 98: 10716–10721.
[9] Loredana Ruggeri, Marusca Capanni, Elena Urbani, et al. Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants. Science, 2002; 295: 2097-2100.
[10] 董陆佳. KIR 基因与异基因造血细胞移植. 中国实验血液学杂志,2004;12(1):108–114.
[11] Roger K Strair, Dale Schaar, Daniel Medina, et al. Antineoplastic Effects of Partially HLA-Matched Irradiated Blood Mononuclear Cells in Patients With Renal Cell Carcinoma. Journal of Clinical Oncology, 2003; 21: 3785-3791
[12] Vogelsang G, B Lee. L Bensen-kennedy, D.M. Pathogenesis and treatment of graft-versus-host disease alter bone marrow transplant. Annu Rex Med,2003;54:29–52.
[13]Falkenburg JH, van de Corput, L, Marijt, E. W. & Willemze, R. Minor histocompatibility antigens in human stem cell transplantation. Exp Hematol, 2003; 31: 743-751.
[14]Frederick, R. Appelbaun. Haematopoietic cell transplantation as immunotherapy. Nature, 2001; 411: 385 – 389.
[15]M Renga, P Pedrazzoli, S Siena. Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors. Annals of Oncology, 2003; 14: 1177-1184.
[16]Adams AB, Durham MM, Kean L, et al. Costimulation blockade, busulfan, and bone marrow promote titratable macrochimerism, induce transplantation tolerance, and correct genetic hemoglobinopathies with minimal myelosuppression. J Immunol, 2001; 167: 1103–1111.
[17] Sophia S. B. Randolph, Theodore A. Gooley, Edus H. Warren, et ql. Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants. Blood, 2004, 103:347-352.
[18]Jason Wynberg, Richard Childs. Evolutions in tumor immunology: Directing allogeneic immune cells against metastatic cancers. Scientific Communications, 2004; 1: 26-29.
[19]Ballen K, Becker P, Emmons R, et al. Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood, 2002; 100(2): 442-450.
[20]Vittorio Montefusco. To the editor: Donor lymphocyte infusions as primary therapy for neoplasms. Karen Ballen, Peter Quesenberry. Response: Low-dose TBI for malignancy: cellular immune therapy .Correspondence. Blood, 2003; 101(1): 373-373.
[21]Rainer F Storb, Guido Lucarelli, Peter A McSweeney, et al. Hematopoietic Cell Transplantation for Benign Hematological Disorders and Solid Tumors. Hematology, 2003; 2003: 372-397.
[22]Moscovitch M, Slavin S. Antitumor effect of allogeneic bone marrow transplantation in (NZB x NZW) F1 hybrids with spontaneous lymphosarcoma. J Immunol, 1984; 132: 997–1003.
[23]Morecki S, Mosshel Y, Gelfand Y, et al. Induction of graft vs tumor effect in a murine model of mammary carcinoma. Int J Cancer, 1997; 71: 59–63.
[24]Morecki S, Yacovlev E, Diab A, Slavin S. Allogeneic cell therapy for murine mammary carcinoma. Cancer Res 1998; 58: 3891–3895
[25]Richard W Childs. Immunotherapy of Solid Tumors: Nonmyeloablative Allogeneic Stem Cell Transplantation. From Medscape General Medicine. Posted 06/26/2002.
[26]Childs R, Chernoff A, Contentin N. et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 2000; 343: 750–758.
[27]Mena O, Igarashi T, Srinivasan R et al. Immunologic mechanisms involved in the graft-vs-tumor (GVT) effect in renal cell carcinoma (RCC) following nonmyeloablative allogeneic peripheral blood stem cell transplantation (NST). Blood, 2001; 98 (Suppl): 856a (Abstr 3555).
[28]Hohler PC, Hank JA, Exten R. et al. Clinical response of a patient with diffuse histiocytic lymphoma to adoptive chemoimmunotherapy using cyclophosphamide and alloactivated haploidentical lymphocytes: A case report and phase I trial. Cancer, 1985; 55: 552-560.
[29]David L Porter, Jean M Connors, Vivianna MD Van Deerlin, Graft-Versus-Tumor Induction With Donor Leukocyte Infusions as Primary Therapy for Patients With Malignancies. Journal of Clinical Oncology, 1999; 17: 1234-1240.
[30]Lu PH,Negrin RS. Anovel population or expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with sever combined immunodeflciency. J Immunol, 1994,153: 1687–1696.
2. Lanier LL. NKcell receptors. Anna Rev Immunol, 1998. 16: 359-393.
3. Garrido F, Ruiz-Cabello F, Cabrera T, et al. Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today, 1997. 18(2): 89-95.
4. Ruiz-Cabello F G F. HLA and cancer: from research to clinlcal impact. Immunol Today, 1998. 19: 539-542.
5. Paul P, Rouas-Freiss N, Khalil-Daher I, et al. HLA-G expression in melanoma: a way for tumor cells to escape from immunosurveillance. Proc Natl Acad Sci U S A, 1998. 95(8): 4510-4515.
6. Carosella E D, Dausset J, Rouas-Freiss N. Transplacental transmission of natural-killer-cell lymphoma. N Engl J Med, 1999. 341(25): 1937.
7. Storb R F, Lucarelli G, McSweeney P A, et al. Hematopoietic cell transplantation for benign hematological disorders and solid tumors. Hematology (Am Soc Hematol Educ Program), 2003: 372-397.
8. Porter D L, Connors J M, Van Deerlin V M, et al. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol, 1999. 17(4): 1234.
9. Collins R H Jr, Shpilberg O, Drobyski W R, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol, 1997. 15(2): 433-444.
10. Mapara M Y, Sykes M. Tolerance and cancer: mechanisms of tumor evasion and strategies for breaking tolerance. J Clin Oncol, 2004. 22(6): 1136-1151.
11. Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science, 2002. 295(5562): 2097-2100.
12. Butcher B W, Collins R H, Jr. The graft-versus-lymphoma effect: clinical review and future opportunities. Bone Marrow Transplant, 2005. 36(1): 1-17.
13. Porter D L. The graft-versus-tumor potential of allogeneic cell therapy: an update on donor leukocyte infusions and nonmyeloablative allogeneic stem cell transplantation. J Hematother Stem Cell Res, 2001. 10(4): 465-480.
14. 韩伟,陆道培,黄晓军,等. HLA 配型不相合造血干细胞移植 GIAC 方案 100 例临床分析. 中华血液学杂志,2004. 25(8): 453-457.
15. 段连宁,郭坤元,褚建新,等. 小鼠红白血病在半相合型小鼠体内的生物特性. 中国实验血液学杂志,2002. 12(1): 108-114.
16. Slavin S, Nagler A, Naparstek E, et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood, 1998. 91(3): 756-763.
17. Gleichmann E, Gleichmann H, Wilke W. Autoimmunization and lymphomagenesis in parent to F1 combinations differing at the major histocompatibility complex: model for spontaneous disease caused by altered self-antigens? Transplant Rev, 1976. 31: 156-224.
18. Carayanniotis G, Halloran P F. Differential resistance to growth of a tumor expressing incompatible minor alloantigens reflects regulatory influences rather than differences in anti-minor-CTL-P frequencies. Cell Immunol, 1985. 91(1): 100-110.
19. Morecki S, Moshel Y, Gelfend Y, et al. Induction of graft vs. tumor effect in a murine model of mammary adenocarcinoma. Int J Cancer, 1997. 71(1): 59-63.
20. Morecki S, Yacovlev E, Diab A, et al. Allogeneic cell therapy for a murine mammary carcinoma. Cancer Res, 1998. 58(17): 3891-3895.
21. Weiss L, Reich S, Slavin S. Allogeneic cell therapy in murine B-cell leukemia (BCL1): 1. Alloimmune-mediated graft-versus-leukemia (GVL) effects induced by unmodified and in vitro rIL-2-activated bone marrow and lymphocytes from different lymphoidcompartments. Cytokines Cell Mol Ther, 1999. 5(3): 145-152.
22. Plytycz B, Seljelid R. Hybrid resistance to the ascites form of the murine sarcoma. Arch Immunol Ther Exp (Warsz), 1987. 35(6): 863-869.
23. Saitoh A, Yasaka N, Osada A, et al. Migration of Langerhans cells in an in vitro organ culture system: IL-6 and TNF-alpha are partially responsible for migration into the epidermis. J Dermatol Sci, 1999. 19(3): 166-174.
24. Pirozhkov A V, Dozmorov I M, Petrov R V. The growth of hemopoietic stem cells is inhibited by natural killers only in the nonsyngeneic microenvironment. Transplantation, 1994. 58(3): 345-349.
25. Shibata Y, Volkman A. Restoration of prostaglandin releasing macrophage populations in lethally irradiated mice with spleen cells from bone marrow-depleted donors. J Leukoc Biol, 1991. 49(4): 397-406.
26. Hui K M, Sim T, Foo T T, et al. Tumor rejection mediated by transfection with allogeneic class I histocompatibility gene. J Immunol, 1989. 143(11): 3835-3843.
27. Skorski T, Kawalec M. Induction of immune resistance against L1210 lymphatic leukemia in mice after chemoradiotherapy of the leukemia and reconstitution with bone marrow purged from the leukemia with mafosfamide. Exp Hematol, 1988. 16(9): 782-784.
28. Vanclee A, Lutgens L C, Oving E B, et al. Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model. Bone Marrow Transplant, 2005. 36(10): 907-915.
29. Rosenstein M, Eberlein T J, and Rosenberg S A, Adoptive immunotherapy of established syngeneic solid tumors: role of T lymphoid subpopulations. J Immunol, 1984. 132(4): 2117-2122.
30. Li J J, Zhang Y, Zhang M W, et al. [Establishment of nonmyeloablative allogeneic stem cell transplantation model in H-2 haploidentical mice and its related study.]. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2004. 12(5): 655-660.
31. Kitajima T, Iwashiro M, Kuribayashi K, et al. The role of CD4+ and CD8+ cells in normal F1 hybrid host in the resistance to lethal graft-versus-host disease induction by transfer of parent spleen cells. Immunol Lett, 1994. 40(3): 207-210.
32. 王剑锋,凌茂英,初海鹰,等. 小鼠腹水型肝癌细胞系(H22 - Fo/ L)的建立及其生物学特性. 中华病理学杂志,1991. 20(1): 65.
33. Zhu B D, Yuan S J, Xu J M, et al. [The effect of IRESSA on H22 mouse hepatocellular carcinoma]. Zhonghua Yi Xue Za Zhi, 2004. 84(8): 684-686.
34. Zhai Y, Lu Z J. Effect of Thalidomide on Tumor Growth in Mouse Hepatoma H22 Mode. Chinese Journal of Cancer, 2003. 22(12): 1301-1306.
35. 李海燕,方肇勤,梁尚华. 小鼠移植性肝癌(H22)模型的研究及在中医药抗肿瘤中的应用. 中国中医基础医学杂志,2000. 6(1): 27-30.
36. LIU Junxu,LU Zhanjun,WANG Xiufang,et al. The Comparison in Cellulate Characteristics among Murine Hepatoma22 Cell Lines from Different Institutes. Chin J Lab Anim Sci, 2001. 11(1): 23-27.
37. 刘军须,吕占军,王秀芳,等. 不同单位小鼠肝癌 H22 瘤株蛋白质组成比较研究. 实验动物科学与管理,2001. 18(1): 11-12.
38. 刘军须,刘福英,王秀芳,等. 小鼠肝癌 H22 克隆细胞株 H2D8 与其原瘤株武汉H22 的基本特性比较研究. 实验动物科学与管理,2002. 19(3): 1-4.
39. LIU Junxu,LIU Fuying,CAI Yuehua,et al. The Comparison in Biological Characteristics among Murine Hepatoma 22 Cell Lines from Different Institutes. Acta Laboratorium Animalis Scicetia Sinica, 2002. 10(1): 43-46.
40. 黄承钰,曾令福,徐亚林,等. 小鼠实体型肝癌 H22 移植实验条件探讨. 临床与实验病理学杂志,1997. 13(2): 188-189.
41. 张学军,潘崚,王福旭,等. 雷公藤甲素治疗异基因骨髓移植后 aGVHD 的实验研究. 中国免疫学杂志,2005. 21(8): 612-616.
42. Morecki S, Yacovlev E, Gelfand Y, et al. Cell therapy with preimmunized effector cells mismatched for minor histocompatible antigens in the treatment of a murine mammarycarcinoma. J Immunother, 2001. 24(2): 114-121.
43. Morecki S, Yacovlev E, Gelfand Y, et al. Allogeneic versus syngeneic killer splenocytes as effector cells for the induction of graft-versus-tumor effect. Biol Blood Marrow Transplant, 2004. 10(1): 40-48.
44. Kummar S, Ishii A, Yang H, et al. Modulation of graft-versus-tumor effects in a murine allogeneic bone marrow transplantation model by tumor-derived transforming growth factor-betaI. Biology of Blood and Marrow Transplantation, 2001. 7: 25-30.
45. 陈字,丁天凌,陈勤奋,等. 非清髓异基因骨髓移植小鼠模型的建立. 上海实验动物科学,2002. 24(2): 81-84.
46. Champlin R, Khouri I, Komblau S, et al. Reinventing bone marrow transplantation. Nonmyeloablative preparative regimens and induction of graft-vs-malignancy effect. Oncology (Williston Park), 1999. 13(5): 621-628; discussion 631, 635-628, 641.
47. Giralt S, Khouri I, and Champlin R, Non myeloablative "mini transplants". Cancer Treat Res, 1999. 101: 97-108.
48. Sandmaier B M, McSweeney P, Yu C, et al. Nonmyeloablative transplants: preclinical and clinical results. Semin Oncol, 2000. 27(2 Suppl 5): 78-81.
49. Peccatori J, Barkholt L, Demirer T, et al. Prognostic factors for survival in patients with advanced renal cell carcinoma undergoing nonmyeloablative allogeneic stem cell transplantation. Cancer, 2005. 104(10): 2099-2103.
50. Ballen K K, Becker P S, Emmons R V, et al. Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood, 2002. 100(2): 442-450.
51. Montefusco V. To the editor: Donor lymphocyte infusions as primary therapy for neoplasms. Karen Ballen, Peter Quesenberry. Response: Low-dose TBI for malignancy: cellular immune therapy.Correspondence. Blood, 2003. 101(1): 373-373.
52. Strair R K, Schaar D, Medina D, et al. Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma. J Clin Oncol,2003. 21(20): 3785-3791.
53. 韦大文,贾玉梅,李中正. 紫金散对 H22 小鼠肝癌实体瘤及腹水瘤抑瘤率的实验研究. 中国中药杂志,2005. 17(9): 1346-1348.
54. Emmenegger U, Man S, Shaked Y, et al. A comparative analysis of low-dose metronomic cyclophosphamide reveals absent or low-grade toxicity on tissues highly sensitive to the toxic effects of maximum tolerated dose regimens. Cancer Res, 2004. 64(11): 3994-4000.
55. Azoulay-Dupuis E, Bedos J P, Mohler J, et al. Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia. Antimicrob Agents Chemother, 2004. 48(4): 1105-1111.
56. Hermans I F, Chong T W, Palmowski M J, et al. Synergistic effect of metronomic dosing of cyclophosphamide combined with specific antitumor immunotherapy in a murine melanoma model. Cancer Res, 2003. 63(23): 8408-8413.
57. LI G-f, CAO J-g, ZHUANG Y-z. Synergetic Effect of Neferina on Cell Apoptosis Induced by Cyclophosphamide in Mice Lewis Lung Carcinoma. The Practical Journal of Cancer, 2005. 20(2): 135-137.
58. Henslee-Downey P J. Allogeneic transplantation across major HLA barriers. Best Pract Res Clin Haematol, 2001. 14(4): 741-754.
59. 张立成,郭坤元,董波,等. γ 射线照射单倍型供者淋巴细胞输注抗白血病作用的实验研究. 中华血液学杂志,2000. 21(2): 81-83.
60. 张立成,郭坤元,罗庆良,等. γ 射线照射预防供者淋巴细胞输注相关移植物抗宿主病的实验研究. 中华血液学杂志,1999. 20(9): 493-495.
61. 陈字,陈波斌,王钦红,等. γ 射线辐照抑制淋巴细胞增殖的剂量—效应关系研究. 中国临床医学,2003. 10(4): 540-541,544.
62. Guerriero A, Boyer M, Waller E, et al. γ irradiation activetes NF-κB in human T cells. The 39th Annual Meeting of Hematology, San Diego, 1997: 37.
63. Igietseme J U, Smith K, Simmons A, et al. Effect of gamma-irradiation on the effectorfunction of T lymphocytes in microbial control. Int J Radiat Biol, 1995. 67(5): 557-564.
64. Waller E, Redei I, Yeager A, et al. 7.5 Gy irradiation attenuates the graft-versus-host disease potential of allogenic lymphocytes while preserving antiluekemic activity in preclinical and clinical studies. Blood, 1997. 90(10 suppl 1): 547a.
65. 董陆佳. KIR 基因与异基因造血细胞移植. 中国实验血液学杂志,2004. 12(1): 108-114.
66. G.施蒂勒,P.瓦尔德编,朱立平,张伟译. 癌症免疫治疗[M].北京:化学工业出版社,2004(第一版): 166,279-289.
67. Renga M, Pedrazzoli P, and Siena S, Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors. Ann Oncol, 2003. 14(8): 1177-1184.
68. 郭亚军主编. 细胞生物学与肿瘤免疫学进展[M]. 北京:军事医学科学出版社, 2000(第一版): 30-39.
69. Matte C, Liu J, Cormier J, et al. Donor APCs are required for maximal GVHD but not for GVL. Nature Medicine, 2004. 10(9): 987-992.
70. Shlomchik W D. Antigen presentation in graft-vs-host disease. Experimental Hematology, 2003. 31(12): 1187-1197.
71. Guinan E, Gribben J, Boussiotis V, et al. Pivotal role of the B7:CD28 pathway in transplantation tolerance and tumor immunity. Blood, 1994. 84(10): 3361-3382.
72. Murphy W, Reynolds C, Tiberghien P, et al. Natural killer cells and bone marrow transplantation. Journal of the National Cancer Institute, 1993. 85(18): 1475-1482.
73. 田志刚,孙汭,William,等. NK 细胞用于肿瘤免疫治疗的研究进展. 中华微生物学和免疫学杂志,2001. 21(2): 239-240.
74. Groh V, Rhinehart R, Secrist H, et al. Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci U S A, 1999. 96(12): 6879-6884.
75. Vivier E, Tomasello E, Paul P. Lymphocyte activation via NKG2D: towards a newparadigm in immune recognition? Curr Opin Immunol, 2002. 14(3): 306-311.
76. Diefenbach A, Tomasello E, Lucas M, et al. Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D. Nat Immunol, 2002. 3(12): 1142-1149.
77. Ho E L, Carayannopoulos L N, Poursine-Laurent, et al. Costimulation of multiple NK cell activation receptors by NKG2D. J Immunol, 2002. 169(7): 3667-3675.
78. Zompi S, Hamerman J A, Ogasawara K, et al. NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases. Nat Immunol, 2003. 4(6): 565-572.
79. Diefenbach A, Jensen E R, Jamieson A M, et al. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature, 2001. 413(6852): 165-171.
80. Liu Y X, Hu G L, Liu M, et al. [Study of the inhibiting effect of anti-NKG2D polyclonal antibody on cytotoxicities of NK and LAK cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2003. 19(3): 257-259.
81. McNerney M E, Lee K M, Zhou P, et al. Role of natural killer cell subsets in cardiac allograft rejection. Am J Transplant, 2006. 6(3): 505-513.
82. Ogasawara K, Benjamin J, Takaki R, et al. Function of NKG2D in natural killer cell-mediated rejection of mouse bone marrow grafts. Nat Immunol, 2005. 6(9): 938-945.
83. Cerwenka A, Bakker A B, McClanahan T, et al. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity, 2000. 12(6): 721-727.
84. Radaev S, Kattah M, Zou Z, et al. Making sense of the diverse ligand recognition by NKG2D. J Immunol, 2002. 169(11): 6279-6285.
85. O'Callaghan C A, Cerwenka A, Willcox B E, et al. Molecular competition for NKG2D: H60 and RAE1 compete unequally for NKG2D with dominance of H60. Immunity, 2001. 15(2): 201-211.
[1]Markus Y, Mapara, Megan Sykes. Tolerance and Cancer: Mechanisms of Tumor Evasion and Strategies for Breaking Tolerance. Journal of Clinical Oncology, 2004; 22: 1136-1151.
[2]Staveley O’Carroll K, Sotomayor E, Montgomery J, et al. Induction of antigen-specific T cell anergy: An early event in the course of tumor progression. Proc Natl Acard Sci USA, 1998; 95: 1178-1183.
[3] Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient. Blood, 1998; 92(10): 3515-3520.
[4] Petersdorf EW, Longton GM, Anasetti C, et al. Association of HLA-C disparity with graft failure after marrow transplantation from unrelated donors. Blood, 1997; 89(5): 1818-1823.
[5] Shizuru JA, Jerabek L, Edwards CT et al. Transplantation of purified hematopoietic stem cells: requirements for overcoming the barriers of allogeneic engraftment. Biol Blood Marrow Transplant, 1996; 2: 3–14
[6] Shizuru JA, Weissman IL, Kernoff R et al. Purified hematopoietic stem cell grafts induce tolerance to alloantigens and can mediate positive and negative T cell selection. Proc Natl Acad Sci USA, 2000; 97: 9555–9560.
[7] Kyba M, Perlingeiro RC, Daley GQ. HoxB4 confers definitive lymphoid-myeloid engraftment potential on embryonic stem cell and yolk sac hematopoietic progenitors. Cell, 2002; 109: 29–37.
[8] Kaufman DS, Hanson ET, Lewis RL, et al. Hematopoietic colony-forming cells derived from human embryonic stem cells. Proc Natl Acad Sci USA, 2001; 98: 10716–10721.
[9] Loredana Ruggeri, Marusca Capanni, Elena Urbani, et al. Effectiveness of Donor Natural Killer Cell Alloreactivity in Mismatched Hematopoietic Transplants. Science, 2002; 295: 2097-2100.
[10] 董陆佳. KIR 基因与异基因造血细胞移植. 中国实验血液学杂志,2004;12(1):108–114.
[11] Roger K Strair, Dale Schaar, Daniel Medina, et al. Antineoplastic Effects of Partially HLA-Matched Irradiated Blood Mononuclear Cells in Patients With Renal Cell Carcinoma. Journal of Clinical Oncology, 2003; 21: 3785-3791
[12] Vogelsang G, B Lee. L Bensen-kennedy, D.M. Pathogenesis and treatment of graft-versus-host disease alter bone marrow transplant. Annu Rex Med,2003;54:29–52.
[13]Falkenburg JH, van de Corput, L, Marijt, E. W. & Willemze, R. Minor histocompatibility antigens in human stem cell transplantation. Exp Hematol, 2003; 31: 743-751.
[14]Frederick, R. Appelbaun. Haematopoietic cell transplantation as immunotherapy. Nature, 2001; 411: 385 – 389.
[15]M Renga, P Pedrazzoli, S Siena. Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors. Annals of Oncology, 2003; 14: 1177-1184.
[16]Adams AB, Durham MM, Kean L, et al. Costimulation blockade, busulfan, and bone marrow promote titratable macrochimerism, induce transplantation tolerance, and correct genetic hemoglobinopathies with minimal myelosuppression. J Immunol, 2001; 167: 1103–1111.
[17] Sophia S. B. Randolph, Theodore A. Gooley, Edus H. Warren, et ql. Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants. Blood, 2004, 103:347-352.
[18]Jason Wynberg, Richard Childs. Evolutions in tumor immunology: Directing allogeneic immune cells against metastatic cancers. Scientific Communications, 2004; 1: 26-29.
[19]Ballen K, Becker P, Emmons R, et al. Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood, 2002; 100(2): 442-450.
[20]Vittorio Montefusco. To the editor: Donor lymphocyte infusions as primary therapy for neoplasms. Karen Ballen, Peter Quesenberry. Response: Low-dose TBI for malignancy: cellular immune therapy .Correspondence. Blood, 2003; 101(1): 373-373.
[21]Rainer F Storb, Guido Lucarelli, Peter A McSweeney, et al. Hematopoietic Cell Transplantation for Benign Hematological Disorders and Solid Tumors. Hematology, 2003; 2003: 372-397.
[22]Moscovitch M, Slavin S. Antitumor effect of allogeneic bone marrow transplantation in (NZB x NZW) F1 hybrids with spontaneous lymphosarcoma. J Immunol, 1984; 132: 997–1003.
[23]Morecki S, Mosshel Y, Gelfand Y, et al. Induction of graft vs tumor effect in a murine model of mammary carcinoma. Int J Cancer, 1997; 71: 59–63.
[24]Morecki S, Yacovlev E, Diab A, Slavin S. Allogeneic cell therapy for murine mammary carcinoma. Cancer Res 1998; 58: 3891–3895
[25]Richard W Childs. Immunotherapy of Solid Tumors: Nonmyeloablative Allogeneic Stem Cell Transplantation. From Medscape General Medicine. Posted 06/26/2002.
[26]Childs R, Chernoff A, Contentin N. et al. Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. N Engl J Med 2000; 343: 750–758.
[27]Mena O, Igarashi T, Srinivasan R et al. Immunologic mechanisms involved in the graft-vs-tumor (GVT) effect in renal cell carcinoma (RCC) following nonmyeloablative allogeneic peripheral blood stem cell transplantation (NST). Blood, 2001; 98 (Suppl): 856a (Abstr 3555).
[28]Hohler PC, Hank JA, Exten R. et al. Clinical response of a patient with diffuse histiocytic lymphoma to adoptive chemoimmunotherapy using cyclophosphamide and alloactivated haploidentical lymphocytes: A case report and phase I trial. Cancer, 1985; 55: 552-560.
[29]David L Porter, Jean M Connors, Vivianna MD Van Deerlin, Graft-Versus-Tumor Induction With Donor Leukocyte Infusions as Primary Therapy for Patients With Malignancies. Journal of Clinical Oncology, 1999; 17: 1234-1240.
[30]Lu PH,Negrin RS. Anovel population or expanded human CD3+CD56+ cells derived from T cells with potent in vivo antitumor activity in mice with sever combined immunodeflciency. J Immunol, 1994,153: 1687–1696.