Abstract LB-380: Novel coupledCARTMtechnology for treating colorectal cancer

作者：Song Li, Chengfei Pu, Zhiyuan Cao, Cheng Lu, Hang Yang, Xi Huang, Xiaogang Shen, Xiuwen Wang, Zhao Wu, Lei Xiao · 发表于：Cancer Research · 年份：2020 · DOI：10.1158/1538-7445.am2020-lb-380 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Cancer Research and Treatments

Abstract Chimeric antigen receptor (CAR) T cell therapy has made significant progress in the treatment of blood cancers such as leukemia, lymphoma, and myeloma. However, the therapy faces many challenges in treating solid tumors. These challenges include physical barriers, tumor microenvironment immunosuppression, tumor heterogeneity, target specificity, and limited reactive cell expansion in vivo. Here, we developed CAR -T cells based on a novel CoupledCARTM technology to treat solid tumors. CoupledCAR T cells significantly improved the expansion of the CAR-T cells in vivo and enhanced the CAR-T cells' migration ability and resistance to immunosuppression by the tumor microenvironment, allowing the CAR-T cells to infiltrate to tumor tissue sites and increase anti-tumor activities.Specifically, we engineered CoupledCAR-T cells with lentiviral vectors encoding an anti-GUCY2C (guanylate cyclase 2C) CAR molecule. To verify the safety and efficacy of CoupledCAR T cells for treating solid tumors, we conducted several clinical trials for different solid tumors, including two patients with colorectal cancer. After the infusion of anti-GUCY2C CoupledCAR T cells, these two patients showed rapid expansion of CoupledCAR T cells and the killing of tumor cells. Spherically, we observed that CoupledCAR T cells expanded significantly in the patients and infiltrated tumor tissue sites, demonstrating enhanced anti-tumor activities. Patient Profile: Patient 1: Male, 55Y, Colon Adenocarcinoma. ...