嵌合抗原受体
胰腺癌
癌症研究
体内
细胞毒性T细胞
抗原
医学
体外
单链可变片段
癌症
免疫学
免疫疗法
抗体
免疫系统
内科学
生物
单克隆抗体
生物技术
生物化学
作者
Hongjia Zhu,Xiaoyan Fang,Israth Jahan Tuhin,Jingwen Tan,Jing Ye,Yujie Jia,Nan Xu,Liqing Kang,Minghao Li,Xiaoyan Lou,Jinge Zhou,Yi‐Ting Wang,Zhiqiang Yan,Lei Yu
标识
DOI:10.1007/s00432-022-04017-x
摘要
Chimeric antigen receptor (CAR) T cell therapy has demonstrated clinical success in treating haematologic malignancies but has not been effective against solid tumours thus far. Trop2 is a tumour-related antigen broadly overexpressed on a variety of tumours and has been reported as a promising target for pancreatic cancers. Our study aimed to determine whether CAR T cells designed with a fully human Trop2-specific single-chain fragment variable (scFv) can be used in the treatment of Trop2-positive pancreatic tumours.We designed Trop2-targeted chimeric antigen receptor engineered T cells with a novel human anti-Trop2 scFv (2F11) and then investigated the cytotoxicity, degranulation, and cytokine secretion profiles of the anti-Trop2 CAR T cells when they were exposed to Trop2 + cancer cells in vitro. We also studied the antitumour efficacy and toxicity of Trop2-specific CAR T cells in vivo using a BxPC-3 pancreatic xenograft model.Trop2-targeted CAR T cells designed with 2F11 effectively killed Trop2-positive pancreatic cancer cells and produced high levels of cytotoxic cytokines in vitro. In addition, Trop2-targeted CAR T cells, which persistently circulate in vivo and efficiently infiltrate into tumour tissues, significantly blocked and even eliminated BxPC-3 pancreatic xenograft tumour growth without obvious deleterious effects observed after intravenous injection into NSG mice. Moreover, disease-free survival was efficiently prolonged.These results show that Trop2-targeted CAR T cells equipped with a fully human anti-Trop2 scFv could be a potential treatment strategy for pancreatic cancer and could be useful for clinical evaluation.
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