Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma.
Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma.
复制标题
DOI：
10.1517/14656566.2011.629187
复制
发表时间：
2011-12
影响因子：
3.2
通讯作者：
Fisher PB
中科院分区：
文献类型：
--
作者：
Wang XY;Zuo D;Sarkar D;Fisher PB
黑色素瘤的发病率持续上升，转移性黑色素瘤患者的预后仍然很差。细胞毒性T淋巴细胞抗原-4(CTLA-4)作为主要的免疫检查点之一，下调T细胞活化途径。通过抗体阻断CTLA-4来增强T细胞的激活，为克服肿瘤诱导的免疫耐受提供了一种新的途径。最近，抗CTLA-4治疗在转移性黑色素瘤患者中显示出显著的临床益处，这导致2011年初美国食品和药物管理局批准了ipilimumab。介绍了CTLA-4阻断增强免疫激活的基本概念、CTLA-4靶向肿瘤免疫治疗的科学基础和临床前证据。我们还提供了抗CTLA-4抑制剂的临床试验的最新进展，并讨论了相关的自身免疫毒性。鉴于总存活率是抗CTLA-4治疗的唯一有效终点，抗原或肿瘤特异性免疫在患者中的临床意义仍有待阐明。需要更多的研究来阐明免疫相关副作用的预后意义，并显著优化治疗方案。对CTLA-4抗体作用机制的更好理解也可能导致这种新疗法在其他肿瘤类型的广泛临床应用。
The incidence of melanoma continues to rise and prognosis in patients with metastatic melanoma remains poor. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) serves as one of the primary immune checkpoints and downregulates T cell activation pathways. Enhancing T cell activation by antibody blockade of the CTLA-4 provides a novel approach to overcome tumor-induced immune tolerance. Recently, anti-CTLA-4 therapy demonstrated significant clinical benefit in patients with metastatic melanoma, which led to the approval of ipilimumab by the Food and Drug Administration in early 2011. The fundamental concepts underlying CTLA-4 blockade-potentiated immune activation, the scientific rationale for and the preclinical evidence supporting CTLA-4-targeted cancer immunotherapy are presented. We also provide an update on clinical trials with anti-CTLA-4 inhibitors and discuss the associated autoimmune toxicity. Given that overall survival is the only validated endpoint for the anti-CTLA-4 therapy, the clinical implications of the antigen or tumor-specific immunity in patients remain to be clarified. Additional research is necessary to elucidate the prognostic significance of immune-related side effects and significantly optimize the treatment regimens. An improved understanding of the mechanisms of action of CTLA-4 antibodies may also culminate in wide-ranging clinical applications of this novel therapy for other tumor types.
登录
查看更多内容
CTLA-4 阻断和 4-1BB 激活相结合，通过增加 T 细胞浸润、增殖和细胞因子产生来增强肿瘤排斥。
影响因子：
3.7
作者：
Curran MA;Kim M;Montalvo W;Al-Shamkhani A;Allison JP
通讯作者：
Allison JP
影响因子：
45.3
作者：
Chapman, PB;Einhorn, LH;Kirkwood, JM
通讯作者：
Kirkwood, JM
影响因子：
45.3
作者：
Balch, Charles M.;Gershenwald, Jeffrey E.;Sondak, Vernon K.
通讯作者：
Sondak, Vernon K.
影响因子：
11.2
作者：
Curran MA;Allison JP
通讯作者：
Allison JP
影响因子：
3.9
作者：
Akhtari, Mojtaba;Waller, Edmund K.;Arellano, Martha L.
通讯作者：
Arellano, Martha L.