Leuci Valeria, Mesiano Giulia, Gammaitoni Loretta, Aglietta Massimo, Sangiolo Dario
Laboratory of Cell Therapy, Institute for Cancer Research and Treatment, Provinciale 142 - 10060 Candiolo, Torino Italy.
Curr Gene Ther. 2014 Feb;14(1):52-62. doi: 10.2174/1566523213666131223130353.
Genetic engineering of T lymphocytes to confer new antitumor specificities is a fascinating approach that may help the successful clinical translation of adoptive immunotherapy strategies. The recognition of tumor-specific antigens may be obtained inducing the membrane expression of transgene encoded antitumor T cell receptors (TCR) or chimeric antigen receptors (CAR). Few but very informative clinical trials with TCR or CAR redirected T lymphocytes have been attempted in the last years, reporting important clinical results along with disappointing failures and important warnings. In this work, we will focus on TCR and CAR redirected T lymphocytes as adoptive immunotherapy for solid tumors. We will review the main topics of these strategies from the angle of clinical applications, discussing the main issues that emerged from early clinical trials and their impact on next study designs.
对T淋巴细胞进行基因工程改造以赋予其新的抗肿瘤特异性,是一种引人入胜的方法,可能有助于过继性免疫治疗策略成功转化至临床应用。通过诱导转基因编码的抗肿瘤T细胞受体(TCR)或嵌合抗原受体(CAR)的膜表达,可实现对肿瘤特异性抗原的识别。在过去几年中,已经尝试了少数但信息丰富的使用TCR或CAR重定向T淋巴细胞的临床试验,报告了重要的临床结果以及令人失望的失败案例和重要警示。在这项工作中,我们将重点关注TCR和CAR重定向T淋巴细胞作为实体瘤过继性免疫治疗的应用。我们将从临床应用的角度回顾这些策略的主要话题,讨论早期临床试验中出现的主要问题及其对后续研究设计的影响。