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首页> 外文期刊>Clinical, Cosmetic and Investigational Dermatology >Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma
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Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

机译：黑色素瘤的抗细胞毒性T淋巴细胞抗原4抗体

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Abstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under investigation in combination with other treatments, such as chemotherapy, target agents, radiotherapy, and other immunotherapeutic regimens.
机译：摘要：旨在增强肿瘤特异性反应的方法为动物模型和人类癌症中免疫疗法的原理提供了证据。伊匹木单抗是一种抗细胞毒性T淋巴细胞抗原4（CTLA-4）抗体，是新一代的免疫治疗剂，在转移性黑色素瘤患者的无病生存和总体生存方面表现出活性。它的使用于2011年3月获得美国食品和药物管理局的批准，用于治疗已扩散或无法通过手术切除的晚期黑色素瘤患者。讨论了CTLA-4抗体在抗肿瘤免疫应答激活中的作用机理，并讨论了ipilimumab在晚期黑素瘤患者中的临床研究。伊匹木单抗治疗已与由于T细胞活化和增殖引起的免疫相关不良事件相关。这些严重的不良反应大多数与胃肠道有关，包括严重的腹泻和结肠炎。在临床研究中探讨了免疫相关不良事件与依普利单抗相关的抗肿瘤活性之间的关系。目前正在研究可预测可用于抗CTLA-4治疗的患者临床反应和生存的生物标志物。除了实体瘤标准中标准反应评估标准所定义的常规反应模式和稳定疾病外，在部分患者中，ipilimumab还显示出临床活动延迟的模式，与整体生存期的改善相关。由于这个原因，已经提出了一套新的肿瘤免疫疗法反应标准，称为免疫相关反应标准。这些新标准目前用于更好地分析免疫治疗方案的临床活性。目前正在研究将伊匹单抗与其他疗法（例如化学疗法，靶向药物，放疗和其他免疫疗法）结合使用。

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