多发性骨髓瘤过继细胞免疫治疗的研究进展_West China Medical Journal

Authors：

钟国成 ,  孙薏

Corresponding author：

孙薏, Email: zgc005@yahoo.com.cn

Keywords：

多发性骨髓瘤; 过继免疫治疗; 树突状细胞; 细胞因子诱导的杀伤细胞

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【摘要】　多发性骨髓瘤（multiple myeloma， MM）是严重威胁健康的恶性浆细胞疾病，主要的治疗方法是传统化学疗法，但其疗效有限，患者生活质量低，预后差。免疫治疗是一种新兴的有望在未来彻底消灭肿瘤细胞的治疗手段，过继细胞免疫治疗（adoptive cellular immunotherapy， ACI）更是经体内及体外都证实了具有强大的抗瘤作用。ACI与其他治疗手段的有机结合和合理安排将对MM的治疗带来新的曙光。现就目前开展的ACI治疗MM的前沿研究予以综述。

Citation： 钟国成,孙薏. 多发性骨髓瘤过继细胞免疫治疗的研究进展. West China Medical Journal, 2011, 26(12): 1805-1809. doi: Copy

1.	Dib A, Barlogie B, Shaugllnessy JD, et al. Methylation and expression of the p16INK4A tumor suppressor gene in multiple myeloma[J]. Blood, 2007, 109(3): 1337-1338.
2.	Anderson KC. From the guest editor: the evolving treatment paradigm in multiple myeloma[J]. Cancer J, 2009, 15(6): 456.
3.	Rosenblatt J, Avigan D. Cellular immunotherapy for multiple myeloma[J].Best Pract Res Clin Haematol, 2008, 21(3): 559-577.
4.	Condomines M, Veyrune JL, Larroque M, et al. Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy[J]. J Immunol, 2010, 184(2): 1079-1084.
5.	Yi Q. Novel immunotherapies[J]. Cancer J, 2009, 15(6): 502-510.
6.	Lokhorst HM, Liebowitz D. Adoptive T-cell therapy[J]. Semin Hematol, 1999, 36(1): 26-29.
7.	Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Dornor leukocyte infusions are effective in multiple myeloma after allogeneic bone marrow transplantation[J]. Blood, 1997, 90(10): 4206-4211.
8.	Deol A, Lum LG. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited[J]. Cancer Treat Rev, 2010, 36(7): 528-538.
9.	Klingemann H, Boissel L. Targeted cellular therapy with natural killer cells[J]. Horm Metab Res, 2008, 40(2): 122-125.
10.	Harnack U, Johnen H, Pecher G. natural killer cell line yt exerts cytotoxicity against CD86+ myeloma cells[J]. Anticancer Res, 2011, 31(2): 475-479.
11.	Alici E, Konstantinidis KV, Sutlu T, et al. Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model[J]. Exp Hematol, 2007, 35(12): 1839-1846.
12.	Zhong G,Wang J,Xu M,et al. Enhanced maturation and functional capacity of dendritic cells induced by mannosylated L2 domain of ErbB2 receptor[J]. Scand J Immunol, 2005, 62(2):108-116.
13.	Linn YC, Hui KM. Cytokine-induced killer cells: NK-like T cells with cytotolytic-specificity against leukemia[J]. Leukemia Lymphoma, 2003, 44(9): 1457-1462.
14.	Eubel J, Enk AH. Dendritic cell vaccination as a treatment modality for melanoma[J]. Expert Rev Anticancer Ther, 2009, 9(11):1631-1642.
15.	Berntsen A, Trepiakas R, Wenandy L, et al. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial[J]. J Immunother, 2008, 31(8): 771-780.
16.	Rozkova D, Tiserova H, Fucíkova J, et al. FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer[J]. Clin Immunol, 2009, 131(1): 1-10.
17.	李纯团, 朱雄鹏, 许文前, 等. 抗原致敏、GM-CSF基因修饰的树突状细胞诱导免疫杀伤多发性骨髓瘤细胞U266的研究[J]. 中国实验血液学杂志, 2009, 17(4): 929-932.
18.	Lee JJ, Choi BH, Kang HK, et al. Induction of multiple myeloma-specific cytotoxic T lymphocyte stimulation by dendritic cell pulsing with purified and optimized myeloma cell lysates[J]. Leuk Lymphoma, 2007, 48(10): 2022-2031.
19.	Cohen S, Haimovich J, Hollander N. Dendritic cell-based therapeutic vaccination against myeloma: vaccine formulation determines efficacy against light chain myeloma[J]. J Immunol, 2009, 182(3): 1667-1673.
20.	Pievani A, Belussi C, Klein C, et al. Enhanced killing of human B-cell lymphoma targets by combined use of cytokine-induced killer cell(CIK)cultures and anti-CD20 antibodies[J]. Blood, 2011, 117(2): 510-518.
21.	Zhao Q, Zhang H, Li Y, et al. Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro[J]. J Exp Clin Cancer Res, 2010, 29:118-130.
22.	Gorschlüter M, Ziske C, Glasmacher A, et al. Current clinical and laboratory strategies to augment the efficacy of immunotherapy in multiple myeloma[J]. Clin Cancer Res, 2001, 7(8): 2195-2204.
23.	Lin J, Zhu H, Lu X, et al. Autologous cytokine-induced killer cells in the treatment of multiple myeloma concomitant with lung cancer and paraneoplastic dermatoses[J]. Intern Med, 2010, 49(21): 2341-2346.
24.	Mrten A, Renoth S, von Lilienfeld-Toal M, et al. Enhanced lytic activity of cytokine-induced killer cells against multiple myeloma cells after co-culture with idiotype-pulsed dendritic cells[J]. Haematologica, 2001, 86(10): 1029-1037.
25.	Su X, Zhang L, Jin L, et al. Coculturing dendritic cells with zoledronate acid efficiently enhance the anti-tumor effects of cytokine-induced killer cells[J]. J Clin Immunol, 2010, 30(5): 766-774.
26.	钟国成, 张小玉, 孙薏, 等. 自体肿瘤抗原致敏的树突状细胞联合细胞因子诱导杀伤细胞应用于肺腺癌治疗的临床研究[J]. 肿瘤, 2010, 30(5): 395-400.
27.	Li H, Wang C, Yu J, et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery[J]. Cytotherapy, 2009, 11(8): 1076-1083.
28.	Rajkumar SV, Rosiol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma[J]. J Clin Oncol, 2008, 26(13): 2171-2177.
29.	Thomas SK, Richards TA, Weber DM. Novel agents for relapsed and/or refractory multiple myeloma[J]. Cancer J, 2009, 15(6): 485-493.
30.	Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs(IMiDS)in multiple myeloma[J]. Leukemia, 2010, 24(1): 22-32.
31.	Ritchie DS, Quach H, Fielding K, et al. Drug-mediated and cellular immunotherapy in multiple myeloma[J]. Immunotherapy, 2010, 2(2): 243-255.
32.	Sharabi A, Laronne-Bar-On A, Meshorer A, et al. Chemoimmunotherapy reduces the progression of multiple myeloma in a mouse model[J]. Cancer Prev Res(Phila), 2010, 3(10): 1265-1276.
33.	Sharabi A, Ghera NH. Breaking tolerance in a mouse model of multiple myeloma by chemoimmunotherapy[J]. Adv Cancer Res, 2010, 107: 1-37.
34.	黄香, 陈龙邦. 化疗药物的免疫调节作用[J]. 医学研究生学报, 2010, 23(1): 76-81.
35.	Frazier JL, Han JE, Lim M, et al. Immunotherapy combined with chemotherapy in the treatment of tumors[J]. Neurosurg Clin N Am, 2010, 21(1): 187-194.
36.	Harrison SJ, Cook G, Nibbs RJ, et al. Immunotherapy of multiple myeloma: the start of a long and tortuous journey[J]. Expert Rev Anticancer Ther, 2006, 6(12): 1769-1785.
37.	Vauleon E, Avril T, Collet B, et al. Overview of cellular immunotherapy for patients with glioblastoma[J]. Clin Dev Immunol, 2010, 2010: 1-18.
38.	Younes A. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma[J]. Hematology Am Soc Hematol Educ Program, 2009: 507-519.

1. 　Dib A, Barlogie B, Shaugllnessy JD, et al. Methylation and expression of the p16INK4A tumor suppressor gene in multiple myeloma[J]. Blood, 2007, 109(3): 1337-1338.
2. 　Anderson KC. From the guest editor: the evolving treatment paradigm in multiple myeloma[J]. Cancer J, 2009, 15(6): 456.
3. 　Rosenblatt J, Avigan D. Cellular immunotherapy for multiple myeloma[J].Best Pract Res Clin Haematol, 2008, 21(3): 559-577.
4. 　Condomines M, Veyrune JL, Larroque M, et al. Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy[J]. J Immunol, 2010, 184(2): 1079-1084.
5. 　Yi Q. Novel immunotherapies[J]. Cancer J, 2009, 15(6): 502-510.
6. 　Lokhorst HM, Liebowitz D. Adoptive T-cell therapy[J]. Semin Hematol, 1999, 36(1): 26-29.
7. 　Lokhorst HM, Schattenberg A, Cornelissen JJ, et al. Dornor leukocyte infusions are effective in multiple myeloma after allogeneic bone marrow transplantation[J]. Blood, 1997, 90(10): 4206-4211.
8. 　Deol A, Lum LG. Role of donor lymphocyte infusions in relapsed hematological malignancies after stem cell transplantation revisited[J]. Cancer Treat Rev, 2010, 36(7): 528-538.
9. 　Klingemann H, Boissel L. Targeted cellular therapy with natural killer cells[J]. Horm Metab Res, 2008, 40(2): 122-125.
10. 　Harnack U, Johnen H, Pecher G. natural killer cell line yt exerts cytotoxicity against CD86+ myeloma cells[J]. Anticancer Res, 2011, 31(2): 475-479.
11. 　Alici E, Konstantinidis KV, Sutlu T, et al. Anti-myeloma activity of endogenous and adoptively transferred activated natural killer cells in experimental multiple myeloma model[J]. Exp Hematol, 2007, 35(12): 1839-1846.
12. 　Zhong G,Wang J,Xu M,et al. Enhanced maturation and functional capacity of dendritic cells induced by mannosylated L2 domain of ErbB2 receptor[J]. Scand J Immunol, 2005, 62(2):108-116.
13. 　Linn YC, Hui KM. Cytokine-induced killer cells: NK-like T cells with cytotolytic-specificity against leukemia[J]. Leukemia Lymphoma, 2003, 44(9): 1457-1462.
14. 　Eubel J, Enk AH. Dendritic cell vaccination as a treatment modality for melanoma[J]. Expert Rev Anticancer Ther, 2009, 9(11):1631-1642.
15. 　Berntsen A, Trepiakas R, Wenandy L, et al. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial[J]. J Immunother, 2008, 31(8): 771-780.
16. 　Rozkova D, Tiserova H, Fucíkova J, et al. FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer[J]. Clin Immunol, 2009, 131(1): 1-10.
17. 　李纯团, 朱雄鹏, 许文前, 等. 抗原致敏、GM-CSF基因修饰的树突状细胞诱导免疫杀伤多发性骨髓瘤细胞U266的研究[J]. 中国实验血液学杂志, 2009, 17(4): 929-932.
18. 　Lee JJ, Choi BH, Kang HK, et al. Induction of multiple myeloma-specific cytotoxic T lymphocyte stimulation by dendritic cell pulsing with purified and optimized myeloma cell lysates[J]. Leuk Lymphoma, 2007, 48(10): 2022-2031.
19. 　Cohen S, Haimovich J, Hollander N. Dendritic cell-based therapeutic vaccination against myeloma: vaccine formulation determines efficacy against light chain myeloma[J]. J Immunol, 2009, 182(3): 1667-1673.
20. 　Pievani A, Belussi C, Klein C, et al. Enhanced killing of human B-cell lymphoma targets by combined use of cytokine-induced killer cell(CIK)cultures and anti-CD20 antibodies[J]. Blood, 2011, 117(2): 510-518.
21. 　Zhao Q, Zhang H, Li Y, et al. Anti-tumor effects of CIK combined with oxaliplatin in human oxaliplatin-resistant gastric cancer cells in vivo and in vitro[J]. J Exp Clin Cancer Res, 2010, 29:118-130.
22. 　Gorschlüter M, Ziske C, Glasmacher A, et al. Current clinical and laboratory strategies to augment the efficacy of immunotherapy in multiple myeloma[J]. Clin Cancer Res, 2001, 7(8): 2195-2204.
23. 　Lin J, Zhu H, Lu X, et al. Autologous cytokine-induced killer cells in the treatment of multiple myeloma concomitant with lung cancer and paraneoplastic dermatoses[J]. Intern Med, 2010, 49(21): 2341-2346.
24. 　Mrten A, Renoth S, von Lilienfeld-Toal M, et al. Enhanced lytic activity of cytokine-induced killer cells against multiple myeloma cells after co-culture with idiotype-pulsed dendritic cells[J]. Haematologica, 2001, 86(10): 1029-1037.
25. 　Su X, Zhang L, Jin L, et al. Coculturing dendritic cells with zoledronate acid efficiently enhance the anti-tumor effects of cytokine-induced killer cells[J]. J Clin Immunol, 2010, 30(5): 766-774.
26. 　钟国成, 张小玉, 孙薏, 等. 自体肿瘤抗原致敏的树突状细胞联合细胞因子诱导杀伤细胞应用于肺腺癌治疗的临床研究[J]. 肿瘤, 2010, 30(5): 395-400.
27. 　Li H, Wang C, Yu J, et al. Dendritic cell-activated cytokine-induced killer cells enhance the anti-tumor effect of chemotherapy on non-small cell lung cancer in patients after surgery[J]. Cytotherapy, 2009, 11(8): 1076-1083.
28. 　Rajkumar SV, Rosiol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma[J]. J Clin Oncol, 2008, 26(13): 2171-2177.
29. 　Thomas SK, Richards TA, Weber DM. Novel agents for relapsed and/or refractory multiple myeloma[J]. Cancer J, 2009, 15(6): 485-493.
30. 　Quach H, Ritchie D, Stewart AK, et al. Mechanism of action of immunomodulatory drugs(IMiDS)in multiple myeloma[J]. Leukemia, 2010, 24(1): 22-32.
31. 　Ritchie DS, Quach H, Fielding K, et al. Drug-mediated and cellular immunotherapy in multiple myeloma[J]. Immunotherapy, 2010, 2(2): 243-255.
32. 　Sharabi A, Laronne-Bar-On A, Meshorer A, et al. Chemoimmunotherapy reduces the progression of multiple myeloma in a mouse model[J]. Cancer Prev Res(Phila), 2010, 3(10): 1265-1276.
33. 　Sharabi A, Ghera NH. Breaking tolerance in a mouse model of multiple myeloma by chemoimmunotherapy[J]. Adv Cancer Res, 2010, 107: 1-37.
34. 　黄香, 陈龙邦. 化疗药物的免疫调节作用[J]. 医学研究生学报, 2010, 23(1): 76-81.
35. 　Frazier JL, Han JE, Lim M, et al. Immunotherapy combined with chemotherapy in the treatment of tumors[J]. Neurosurg Clin N Am, 2010, 21(1): 187-194.
36. 　Harrison SJ, Cook G, Nibbs RJ, et al. Immunotherapy of multiple myeloma: the start of a long and tortuous journey[J]. Expert Rev Anticancer Ther, 2006, 6(12): 1769-1785.
37. 　Vauleon E, Avril T, Collet B, et al. Overview of cellular immunotherapy for patients with glioblastoma[J]. Clin Dev Immunol, 2010, 2010: 1-18.
38. 　Younes A. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma[J]. Hematology Am Soc Hematol Educ Program, 2009: 507-519.

West China Medical Journal

多发性骨髓瘤过继细胞免疫治疗的研究进展

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