Ribas Antoni, Butterfield Lisa H, Glaspy John A, Economou James S
Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, 90095-1782, USA.
J Clin Oncol. 2003 Jun 15;21(12):2415-32. doi: 10.1200/JCO.2003.06.041.
This article reviews the immunologic basis of clinical trials that test means of tumor antigen recognition and immune activation, with the goal to provide the clinician with a mechanistic understanding of ongoing cancer vaccine and cellular immunotherapy clinical trials. Multiple novel immunotherapy strategies have reached the stage of testing in clinical trials that were accelerated by recent advances in the characterization of tumor antigens and by a more precise knowledge of the regulation of cell-mediated immune responses. The key steps in the generation of an immune response to cancer cells include loading of tumor antigens onto antigen-presenting cells in vitro or in vivo, presenting antigen in the appropriate immune stimulatory environment, activating cytotoxic lymphocytes, and blocking autoregulatory control mechanisms. This knowledge has opened the door to antigen-specific immunization for cancer using tumor-derived proteins or RNA, or synthetically generated peptide epitopes, RNA, or DNA. The critical step of antigen presentation has been facilitated by the coadministration of powerful immunologic adjuvants, the provision of costimulatory molecules and immune stimulatory cytokines, and the ability to culture dendritic cells. Advances in the understanding of the nature of tumor antigens and their optimal presentation, and in the regulatory mechanisms that govern the immune system, have provided multiple novel immunotherapy intervention strategies that are being tested in clinical trials.
本文回顾了检测肿瘤抗原识别和免疫激活方法的临床试验的免疫学基础，目的是让临床医生对正在进行的癌症疫苗和细胞免疫治疗临床试验有一个机制性的理解。多种新型免疫治疗策略已进入临床试验阶段，这些试验因肿瘤抗原表征方面的最新进展以及对细胞介导免疫反应调节的更精确认识而加速推进。对癌细胞产生免疫反应的关键步骤包括在体外或体内将肿瘤抗原加载到抗原呈递细胞上，在适当的免疫刺激环境中呈递抗原，激活细胞毒性淋巴细胞，以及阻断自身调节控制机制。这些知识为使用肿瘤衍生蛋白或RNA、或合成产生的肽表位、RNA或DNA进行癌症的抗原特异性免疫接种打开了大门。强大的免疫佐剂的共同给药、共刺激分子和免疫刺激细胞因子的提供以及培养树突状细胞的能力，促进了抗原呈递这一关键步骤。对肿瘤抗原的性质及其最佳呈递方式的理解，以及对免疫系统调节机制的理解取得的进展，提供了多种正在临床试验中进行测试的新型免疫治疗干预策略。
