Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Curr Opin Biotechnol. 2017 Dec;48:142-152. doi: 10.1016/j.copbio.2017.03.024. Epub 2017 May 8.
Immunotherapies are yielding effective treatments for several previously untreatable cancers. Until recently, vaccines and adoptive cell therapies have been designed to target public tumor antigens common to multiple patients rather than private antigens specific to a single patient. Due to the difficulty of identifying public antigens that are expressed exclusively on tumor cells, these studies have yielded both clinical successes and serious immune-related adverse events. Multiple avenues of research now underscore the centrality of tumor-specific mutated private antigens to endogenous anti-tumor immunity. Immunotherapies that target these neoantigens may enable safer and more durable tumor regression, but personalized targeting presents a number of challenges. Foremost among these is to develop processes that accelerate advancement from neoantigen discovery to use of these neoantigens as vaccines or as targets for adoptive cell therapies. Exome sequencing has facilitated discovery of neoantigens for melanoma and other highly mutated cancers. New technologies - possibly proceeding from T cell receptor repertoire sequencing - are needed to identify antigens for cancers with low mutational burden and few neoantigens. In this review, we discuss progress toward personalizing T cell-mediated immunotherapy for cancer as well as challenges going forward.
免疫疗法为多种以前无法治疗的癌症提供了有效的治疗方法。直到最近，疫苗和过继细胞疗法的设计目的是针对多个患者共有的公共肿瘤抗原，而不是针对单个患者的特定抗原。由于识别仅在肿瘤细胞上表达的公共抗原具有挑战性，这些研究取得了临床成功和严重的免疫相关不良事件。现在有多种研究途径强调肿瘤特异性突变的私人抗原对内源性抗肿瘤免疫的核心作用。针对这些新抗原的免疫疗法可能能够更安全、更持久地使肿瘤消退，但个性化靶向存在许多挑战。其中最重要的是开发能够加速从新抗原发现到将这些新抗原用作疫苗或过继细胞疗法靶点的过程。外显子组测序促进了黑色素瘤和其他高度突变癌症的新抗原发现。需要新技术（可能来自 T 细胞受体库测序）来鉴定突变负担低且新抗原少的癌症的抗原。在这篇综述中，我们讨论了为癌症进行个体化 T 细胞介导的免疫疗法的进展以及未来的挑战。
