Greten T F, Jaffee E M
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2196, USA.
J Clin Oncol. 1999 Mar;17(3):1047-60. doi: 10.1200/JCO.1999.17.3.1047.
It has been more than 100 years since the first reported attempts to activate a patient's immune system to eradicate developing cancers. Although a few of the subsequent vaccine studies demonstrated clinically significant treatment effects, active immunotherapy has not yet become an established cancer treatment modality. Two recent advances have allowed the design of more specific cancer vaccine approaches: improved molecular biology techniques and a greater understanding of the mechanisms involved in the activation of T cells. These advances have resulted in improved systemic antitumor immune responses in animal models. Because most tumor antigens recognized by T cells are still not known, the tumor cell itself is the best source of immunizing antigens. For this reason, most vaccine approaches currently being tested in the clinics use whole cancer cells that have been genetically modified to express genes that are now known to be critical mediators of immune system activation. In the future, the molecular definition of tumor-specific antigens that are recognized by activated T cells will allow the development of targeted antigen-specific vaccines for the treatment of patients with cancer.
自首次报道尝试激活患者免疫系统以根除正在发展的癌症以来，已经过去了100多年。尽管随后的一些疫苗研究显示出具有临床意义的治疗效果，但主动免疫疗法尚未成为一种既定的癌症治疗方式。最近的两项进展使得能够设计出更具特异性的癌症疫苗方法：改进的分子生物学技术以及对T细胞激活所涉及机制的更深入理解。这些进展已在动物模型中产生了改善的全身抗肿瘤免疫反应。由于大多数被T细胞识别的肿瘤抗原仍不为人所知，肿瘤细胞本身是免疫抗原的最佳来源。因此，目前在临床上测试的大多数疫苗方法都使用经过基因改造以表达现在已知为免疫系统激活关键介质的基因的全癌细胞。未来，被激活的T细胞识别的肿瘤特异性抗原的分子定义将有助于开发用于治疗癌症患者的靶向抗原特异性疫苗。
