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

用于癌症过继细胞治疗的综合治疗性 T 细胞受体筛选平台

基本信息

批准号：
10480064
负责人：
Ning Jenny Jiang
金额：
$ 33.52万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-04 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10480064
关键词：
Adoptive Cell Transfers Affinity Animal Model Antigen Targeting Antigens Area Blood donor CD8-Positive T-Lymphocytes CTAG1 gene Cancer cell line Cell Culture Techniques Cell Line Cell physiology Cells Clinical Clinical Research Clinical Trials Elements Epitopes Foundations Future Gene Expression Genes Goals Human Immunotherapy In Situ KRASG12D Libraries Magic Malignant Neoplasms Manuscripts Measurement Membrane Memorial Sloan-Kettering Cancer Center Methods Mus Mutate Mutation Names Organoids Patients Process Protein Engineering Research Sampling Speed Surface Plasmon Resonance T-Cell Receptor T-Lymphocyte Technology Testing Therapeutic Tumor Antigens Validation base cancer cell cancer immunotherapy clinical practice combinatorial cross reactivity cytotoxicity cytotoxicity test driver mutation effectiveness testing efficacy testing individual patient neoantigens patient screening peripheral blood pre-clinical prevent screening success technology development therapeutic evaluation tool tumor

项目摘要

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.

摘要最近基于T细胞受体的过继细胞转移疗法的成功产生了新的兴奋，这种治疗方法。然而，缺乏高通量筛选天然存在的高表达的方法，亲和治疗性T细胞受体（TCR）已经限制了这种方法可以广泛应用于不同疾病的程度。各种癌症和大范围的患者。在这项研究中，我们建议开发一个集成平台，一方面大大加快了治疗性TCR的鉴定和测试，另一方面，常见的癌抗原和HLA在肿瘤样品中以单细胞水平表达。我们称之为魔术帽，用高亲和力TCR进行癌症匹配抗原鉴定。该项目的成功打破了在过继细胞转移中鉴定和测试天然存在的治疗性高亲和力TCR的瓶颈一个大的癌症抗原表位组的治疗设置。它可以实现一种新的功能， TCR重定向T细胞中的TCR用于癌症中的过继细胞转移疗法。