Immunotherapy of melanoma with the immune costimulatory monoclonal antibodies targeting CD137.
Immunotherapy of melanoma with the immune costimulatory monoclonal antibodies targeting CD137.
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DOI：
10.2147/cpaa.s46199
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发表时间：
2013-09-02
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Li SY;Liu Y
关于免疫系统如何识别和尝试控制癌症生长和发展的知识已经有了显著的提高。针对癌症的免疫疗法的出现导致了强大的临床反应，并证实了免疫系统可以显着抑制肿瘤的进展。直到最近，转移性黑色素瘤还是一种治疗选择有限、预后不佳的疾病。CD137(又称4-1BB)是肿瘤坏死因子受体超家族的成员，是一种活化诱导的T细胞共刺激分子。越来越多的证据表明，抗CD137单抗具有很强的抗肿瘤活性，这是因为它能够激活CD8+T细胞，产生干扰素-γ，并诱导细胞溶解标志。抗CD137与其他抗癌药物联合治疗，如放射治疗，对非免疫原性或免疫原性差的肿瘤具有强大的肿瘤消退能力。重要的是，以CD137为靶点可以消除已建立的肿瘤，而抗CD137治疗与其他抗癌药物和/或放射治疗协同作用以根除非免疫原性和弱免疫原性肿瘤是另一个好处。目前，人源化的抗CD137抗体BMS-663513正在对实体肿瘤患者进行临床试验，包括黑色素瘤、肾癌、卵巢癌和B细胞恶性肿瘤。在这篇综述中，我们讨论了靶向CD137在肿瘤治疗中的治疗潜力的基础，特别是BMS-663513作为一种免疫共刺激单抗用于黑色素瘤的免疫治疗。
Knowledge of how the immune system recognizes and attempts to control cancer growth and development has improved dramatically. The advent of immunotherapies for cancer has resulted in robust clinical responses and confirmed that the immune system can significantly inhibit tumor progression. Until recently, metastatic melanoma was a disease with limited treatment options and a poor prognosis. CD137 (also known as 4-1BB) a member of the tumor necrosis factor (TNF) receptor superfamily, is an activation-induced T cell costimulator molecule. Growing evidence indicates that anti-CD137 monoclonal antibodies possess strong antitumor properties, the result of their powerful capability to activate CD8+ T cells, to produce interferon (IFN)-γ, and to induce cytolytic markers. Combination therapy of anti-CD137 with other anticancer agents, such as radiation, has robust tumor-regressing abilities against nonimmunogenic or poorly immunogenic tumors. Of importance, targeting CD137 eliminates established tumors, and the fact that anti-CD137 therapy acts in concert with other anticancer agents and/or radiation therapy to eradicate nonimmunogenic and weakly immunogenic tumors is an additional benefit. Currently, BMS-663513, a humanized anti-CD137 antibody, is in clinical trials in patients with solid tumors, including melanoma, renal carcinoma, ovarian cancer, and B-cell malignancies. In this review, we discuss the basis of the therapeutic potential of targeting CD137 in cancer treatment, focusing in particular, on BMS-663513 as an immune costimulatory monoclonal antibody for melanoma immunotherapy.