An integrated therapeutic T cell receptor screening platform for adoptive cell therapy in cancer

摘要 最近基于T细胞受体的过继细胞转移治疗的成功引起了新的兴奋 这种治疗方法。然而，缺乏一种高通量的筛选自然发生的高通量的方法。 亲和力治疗性T细胞受体(TCR)限制了这种方法在不同疾病中的应用范围 癌症种类繁多，患者众多。在本研究中，我们建议开发一个集成平台，该平台 一方面极大地加快了治疗性TCR的识别和测试，另一方面，配置文件 肿瘤标本中常见的肿瘤抗原和HLAs在单细胞水平表达。我们给它取名魔法帽是因为 高亲和力TCRs在癌症配型抗原鉴定中的应用这个项目的成功打破了 过继细胞转移中识别和检测自然产生的治疗性高亲和力TCR的瓶颈 一大批癌症抗原表位的治疗环境。它启用了一种新的功能，可以结合使用 TCR重定向T细胞中的TCRs用于癌症过继细胞转移治疗。

Abstract Recent successes of T cell receptor based adoptive cell transfer therapy have generated new excitement about this therapeutic approach. However, lacking a high-throughput method of screening of naturally occurring high- affinity therapeutic T cell receptors (TCRs) has put a limit on how widely this approach can be applied to different kinds of cancers and a large range of patients. In this study, we propose to develop an integrated platform that on one hand drastically speeds up the identification and test of therapeutic TCRs and on the other hand, profiles common cancer antigens and HLAs expressed in tumor sample at single cell level. We name it Magic-HAT for Matching antigen identification in cancer with High-Affinity TCRs. The success of this project breaks the bottleneck of identifying and testing naturally occurring therapeutic high-affinity TCRs in adoptive cell transfer therapy setting for a large panel of cancer antigen epitopes. It enables a new capability on using combination of TCRs in TCR-redirected T cells for adoptive cell transfer therapy in cancer.