Peggs Karl S, Quezada Sergio A, Korman Alan J, Allison James P
Howard Hughes Medical Institute, Department of Immunology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Curr Opin Immunol. 2006 Apr;18(2):206-13. doi: 10.1016/j.coi.2006.01.011. Epub 2006 Feb 7.
Cytotoxic T lymphocyte antigen-4 has become recognized as one of the key negative regulators of adaptive immune responses, having a central role in the maintenance of peripheral tolerance and in shaping the repertoire of emergent T cell responses. Concurrent recognition of the potential importance of inhibitory immune regulators in limiting antitumor responses, either as a result of chronic antigenic stimulation or the self-nature of many tumor-selective target antigens, has led to the development of cytotoxic T lymphocyte antigen-4-blocking antibodies as therapeutic anticancer agents. Following extensive preclinical modeling, these agents have entered clinical trials, where they are showing encouraging activity in heavily pretreated patients with advanced-stage disease, particularly with melanoma or renal carcinoma. Finding ways to dissociate antitumor activity from adverse immune events should enable actualization of their therapeutic potential in the coming years.
细胞毒性T淋巴细胞抗原4已被公认为适应性免疫反应的关键负调节因子之一，在维持外周免疫耐受和塑造新出现的T细胞反应库中发挥核心作用。由于慢性抗原刺激或许多肿瘤选择性靶抗原的自身性质，人们同时认识到抑制性免疫调节因子在限制抗肿瘤反应中的潜在重要性，这促使了细胞毒性T淋巴细胞抗原4阻断抗体作为治疗性抗癌药物的开发。经过广泛的临床前模型研究，这些药物已进入临床试验阶段，在晚期疾病的重度预处理患者中显示出令人鼓舞的活性，尤其是黑色素瘤或肾癌患者。找到将抗肿瘤活性与不良免疫事件分离的方法，有望在未来几年实现其治疗潜力。
