多發性骨髓瘤過繼細胞免疫治療的研究進展_《華西醫學》

作者：

鐘國成 ,  孫薏

解放軍第452醫院血液腫瘤中心（成都，610021）;

關鍵詞：

多發性骨髓瘤過繼免疫治療樹突狀細胞細胞因子誘導的殺傷細胞

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【摘要】　多發性骨髓瘤（multiple myeloma， MM）是嚴重威脅健康的惡性漿細胞疾病，主要的治療方法是傳統化學療法，但其療效有限，患者生活質量低，預后差。免疫治療是一種新興的有望在未來徹底消滅腫瘤細胞的治療手段，過繼細胞免疫治療（adoptive cellular immunotherapy， ACI）更是經體內及體外都證實了具有強大的抗瘤作用。ACI與其他治療手段的有機結合和合理安排將對MM的治療帶來新的曙光。現就目前開展的ACI治療MM的前沿研究予以綜述。

引用本文： 鐘國成,孫薏. 多發性骨髓瘤過繼細胞免疫治療的研究進展. 華西醫學, 2011, 26(12): 1805-1809. doi: 復制

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.	李純團, 朱雄鵬, 許文前, 等. 抗原致敏、GM-CSF基因修飾的樹突狀細胞誘導免疫殺傷多發性骨髓瘤細胞U266的研究[J]. 中國實驗血液學雜志, 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.	鐘國成, 張小玉, 孫薏, 等. 自體腫瘤抗原致敏的樹突狀細胞聯合細胞因子誘導殺傷細胞應用于肺腺癌治療的臨床研究[J]. 腫瘤, 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.	黃香, 陳龍邦. 化療藥物的免疫調節作用[J]. 醫學研究生學報, 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. 　李純團, 朱雄鵬, 許文前, 等. 抗原致敏、GM-CSF基因修飾的樹突狀細胞誘導免疫殺傷多發性骨髓瘤細胞U266的研究[J]. 中國實驗血液學雜志, 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. 　鐘國成, 張小玉, 孫薏, 等. 自體腫瘤抗原致敏的樹突狀細胞聯合細胞因子誘導殺傷細胞應用于肺腺癌治療的臨床研究[J]. 腫瘤, 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. 　黃香, 陳龍邦. 化療藥物的免疫調節作用[J]. 醫學研究生學報, 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.

《華西醫學》

多發性骨髓瘤過繼細胞免疫治療的研究進展

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《華西醫學》

多發性骨髓瘤過繼細胞免疫治療的研究進展

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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