靶向CD47的抗肿瘤抗体研究进展

doi:10.3760/cma.j.issn.1673422X.2013.11.005

摘要/Abstract

摘要： CD47是个多能分子，在肿瘤细胞逃避免疫监视过程中扮演重要角色，阻断CD47信号通道能有效激发巨噬细胞对肿瘤细胞的吞噬作用，成为非常有前景的肿瘤免疫治疗新途径。靶向CD47的单克隆抗体已成为近年来研究的新热点，目前的实验进展顺利，有必要进行更详尽的研究，使其早日进入临床应用。

关键词: 肿瘤, 抗体, 吞噬作用

Abstract: CD47 is a pluripotent molecule which plays a key role in the process of tumor immune escape. Blocking CD47 signal pathway can activate the macrophages to phagocytose tumor cells, which becomes a promising way for tumor immunotherapy. Monoclonal antibodies targeting CD47 have been the new focus during recent years. Present researches are carried out successfully, however it still needs more work before the clinical application of monoclonal antibodies targeting CD47.

Key words: Neoplasms, Antibodys, Phagocytosis

王玉树, 周兆平, 苏庆宁. 靶向CD47的抗肿瘤抗体研究进展[J]. 国际肿瘤学杂志, 2013, 40(11): 817-820.

WANG Yu-Shu, ZHOU Zhao-Ping, SU Qing-Ning. Anti tumor antibodies targeting CD47[J]. Journal of International Oncology, 2013, 40(11): 817-820.

参考文献

［1］ Chao MP, Majeti R， Weissman IL. Programmed cell removal: a new obstacle in the road to developing cancer. Nat Rev Cancer, 2012,12(1): 58-67. ［2］ Sick E, Jeanne A, Schneider C, et al. CD47 update: a multifaceted actor in the tumor microenvironment of potential therapeutic interest. Br J Pharmacol, 2012,167(7):1415-1430. ［3］ Chao MP, Jaiswal S, WeissmanTsukamoto R, et al. Calreticulin is the dominant prophagocytic signal on multiple human cancers and is counterbalanced by CD47. Sci Transl Med, 2010,2(63)：63ra94. ［4］ Jaiswal S, Chao MP, Majeti R, et al. Macrophages as mediators of tumor immunosurveillance. Trends Immunol, 2010,31(6):212-219. ［5］ Chao MP, Weissman IL, Majeti R. The CD47SIRPα pathway in cancer immune evasion and potential therapeutic implications. Curr Opin Immunol, 2012,24(2):225-232. ［6］ Majeti R, Chao MP, Alizadeh AA, et al. CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells. Cell, 2009,138(2):286-299. ［7］ Sagawa M, Shimizu T, Fukushima N, et al. A new disulfidelinked dimer of a singlechain antibody fragment against human CD47 induces apoptosis in lymphoid malignant cells via the hypoxia inducible factor1α pathway. Cancer Sci, 2011,102(6):1208-1215. ［8］ Chao MP, Alizadeh AA, Tang C, et al. Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer Res, 2010,71(4):1374-1384. ［9］ Chao MP, Alizadeh AA, Tang C, et al. AntiCD47 antibody synergizes with rituximab to promote phagocytosis and eradicate nonHodgkin lymphoma. Cell, 2010,142(5):699-713. ［10］ Chao MP, Tang C, Pachynski RK, et al. Extranodal dissemination of nonHodgkin lymphoma requires CD47 and is inhibited by antiCD47 antibody therapy. Blood, 2011,118(18):4890-4901. ［11］ Kim D, Wang J, Willingham SB, et al. AntiCD47 antibodies promote phagocytosis and inhibit the growth of human myeloma cells. Leukemia, 2012,26(12):2538-2545. ［12］ Edris B, Weiskopf K, Weissman IL, et al. Flipping the script on macrophages in leiomyosarcoma. Oncoimmunology, 2012,1(7):1202-1204. ［13］ Edris B, Weiskopf K, Volkmer AK, et al. Antibody therapy targeting the CD47 protein is effective in a model of aggressive metastatic leiomyosarcoma. Proc Natl Acad Sci USA, 2012,109(17):6656-6661. ［14］ Sick E, Boukhari A, Deramaudt T, et al. Activation of CD47 receptors causes proliferation of human astrocytoma but not normal astrocytes via an aktdependent pathway. Glia, 2011,59(2):308-319. ［15］ Zhao XW, van Beek EM, Schornagel K, et al. CD47signal regulatory protein α (SIRPα) interactions form a barrier for antibodymediated tumor cell destruction. Proc Natl Acad Sci USA, 2011,108(45):18342-18347. ［16］ Willingham SB, Volkmer JP, Gentles AJ, et al. The CD47signal regulatory protein alpha (SIRPα) interaction is a therapeutic target for human solid tumors. Proc Natl Acad Sci USA, 2012,109(17):6662-6667. ［17］ Hongrapipat J, Kopeckova P, Liu J, et al. Combination chemotherapy and photodynamic therapy with Fab′fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells. Mol Pharm, 2008,5(5):696-709. ［18］ Chan KS, Espinosa I, Chao M, et al. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumorinitiating cells. Proc Natl Acad Sci USA, 2009,106(33):14016-14021. ［19］ Kim MJ, Lee JC, Lee JJ, et al. Association of CD47 with natural killer cellmediated cytotoxicity of headandneck squamous cell carcinoma lines. Tumour Biol, 2008,29(1):28-34.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志. 宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.