新生抗原肿瘤治疗性疫苗进展评述

Progress of neoantigen tumor therapeutic vaccine

肿瘤新生抗原是指由肿瘤细胞的基因组突变产生的新生表位免疫原,是一类肿瘤特异性抗原。肿瘤新生抗原比肿瘤相关抗原免疫原性高,没有产生自身免疫应答的风险,是一类极具吸引力的肿瘤治疗性疫苗的抗原。随着新一代测序技术的发展,基于新生抗原的肿瘤治疗性疫苗在过去5年中获得了突破性的进展,呈现出极好的临床前景。本文首先简述新生抗原的免疫学特点,然后展示了新生抗原特异性T细胞应答是抗肿瘤的核心驱动力的证据,最后介绍了新生抗原疫苗的临床前景和临床研究的最新进展,并提出了该领域目前存在的问题和挑战。

Tumor neoantigens, neoepitopes arising from the somatic mutation in the cancer genome, are a class of tumor-specific antigens(TSA). Neoantigens with lower risk of autoimmunity are less likely to be subject to central immune tolerance and therefore are attractive as antigens in tumor therapeutic vaccines. In the past five years, with the development of next generation sequencing technology, the neoantigen-based tumor therapeutic vaccine has made a breakthrough progress and is showing excellent prospects in clinical. In this review, we describe the immunological characteristics of neoantigens, and then present the emerging evidence that neoantigen-specific T cell responses are the dominant driver force for clinical benefit in cancer immunotherapy. At last, we elaborate the recent pre-clinical and clinical progress of neoantigen tumor therapeutic vaccine and highlight the problems and challenges in this field.