CAR T cells equipped with a fully human scFv targeting Trop2 can be used to treat pancreatic cancer

• Published in: Journal of cancer research and clinical oncology Vol. 148; no. 9; pp. 2261 - 2274
• Main Authors: Zhu, Hongjia, Fang, Xiaoyan, Tuhin, Israth Jahan, Tan, Jingwen, Ye, Jing, Jia, Yujie, Xu, Nan, Kang, Liqing, Li, Minghao, Lou, XiaoYan, Zhou, Jing-e, Wang, Yiting, Yan, Zhiqiang, Yu, Lei
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022; Springer Nature B.V
• Subjects: Animals; Antigens; Antigens, Neoplasm; Blood cancer; Cancer Research; Cell Line, Tumor; Cell therapy; Chimeric antigen receptors; Cytokines; Cytotoxicity; Degranulation; Hematology; Humans; Immunotherapy, Adoptive - methods; Internal Medicine; Intravenous administration; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Mice; Oncology; Original Article – Cancer Research; Original – Cancer Research; Pancreatic cancer; Pancreatic Neoplasms - therapy; Receptors, Chimeric Antigen; Solid tumors; T-Lymphocytes; Tumors; Xenograft Model Antitumor Assays; Xenografts; Chimeric antigen receptor T cells; Pancreatic cancer; Trop2; Single chain variable fragment
• ISSN: 0171-5216; 1432-1335; 1432-1335
• DOI: 10.1007/s00432-022-04017-x

Purpose 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. Methods 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. Results 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. Conclusion 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.