Robert Caroline, Ghiringhelli Francois
Institute Gustave Roussy, 94805 Villejuif Cedex, France.
Oncologist. 2009 Aug;14(8):848-61. doi: 10.1634/theoncologist.2009-0028. Epub 2009 Aug 1.
With increasing knowledge of the molecular basis of the immune system and mechanisms of tumor tolerance, novel approaches to treating malignant diseases refractory to standard therapies are being investigated. Monoclonal antibodies (mAbs) that bind cytotoxic T lymphocyte-associated antigen (CTLA)-4 can block inhibitory signals normally generated through this receptor, thus prolonging and sustaining T-cell activation and proliferation. These antibodies are being developed and tested in patients with metastatic melanoma. This article reviews data published or presented at scientific congresses describing the clinical safety and antitumor activity of two different anti-CTLA-4 mAbs: tremelimumab (CP-675,206) and ipilimumab (MDX-010). Overall, although the response rate has not been consistently higher than the response rates associated with other treatments, the induction of durable responses and the favorable safety profile observed with anti-CTLA-4 mAbs are encouraging. However, the true advantage of these new drugs may depend largely on the characterization of predictive biomarkers of activity and subsequent targeting of responsive patients.
随着对免疫系统分子基础和肿瘤耐受机制的了解不断增加，正在研究针对标准疗法难治的恶性疾病的新治疗方法。结合细胞毒性T淋巴细胞相关抗原（CTLA）-4的单克隆抗体（mAb）可阻断通常通过该受体产生的抑制信号，从而延长并维持T细胞的激活和增殖。这些抗体正在转移性黑色素瘤患者中进行研发和测试。本文综述了在科学大会上发表或展示的数据，这些数据描述了两种不同的抗CTLA-4单克隆抗体：曲美木单抗（CP-675,206）和伊匹木单抗（MDX-010）的临床安全性和抗肿瘤活性。总体而言，尽管应答率并不始终高于其他治疗方法的应答率，但抗CTLA-4单克隆抗体所观察到的持久应答诱导和良好的安全性令人鼓舞。然而，这些新药的真正优势可能在很大程度上取决于活性预测生物标志物的特征以及随后对有反应患者的靶向治疗。
