Neo-epitopes derived from mutated tumor suppressor gene RNF43 as targets for adoptive T cell therapy in pancreatic cancer (P17)

源自突变抑癌基因 RNF43 的新表位作为胰腺癌过继性 T 细胞治疗的靶标 (P17)

• 批准号: 404523684
• 金额: --
• 依托单位: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404523684?language=en
• 关键词: Neo; epitopes; derived; mutated; tumor

We investigate cell therapy with T cell receptor (TCR)-engineered T cells in PDAC. Very rare TCRs specific to PDAC neoantigens are isolated from healthy donors and re-expressed in primary T cells via CRISPR/Cas9-mediated T cell engineering. Engineered T cells will be evaluated for their in vitro and in vivo functionality using PDAC cell lines and organoids carrying the mutations of interest. PDAC tumor microenvironment will be analyzed to further improve TCR therapy by T cell co-engineering. In parallel, we will transfer the CRISPR/Cas9-mediated T cell engineering technology into GMP-compliant processes for T cell manufacturing, and attempt to test first T cell products clinically.

我们研究了在PDAC中使用T细胞受体（TCR）工程化T细胞的细胞疗法。从健康供体中分离出对PDAC新抗原特异性的非常罕见的TCR，并通过CRISPR/Cas9介导的T细胞工程在原代T细胞中重新表达。将使用携带感兴趣突变的PDAC细胞系和类器官来评估工程化T细胞的体外和体内功能。将分析PDAC肿瘤微环境以通过T细胞共工程进一步改善TCR疗法。与此同时，我们将把CRISPR/Cas9介导的T细胞工程技术转移到符合GMP的T细胞制造工艺中，并尝试对首批T细胞产品进行临床测试。