Abstract LB-380: Novel coupledCARTMtechnology for treating colorectal cancer

摘要: Chimeric antigen receptor (CAR) T cell therapy has made significant progress in the treatment of blood cancers such as leukemia, lymphoma, and myeloma. However, faces many challenges treating solid tumors. These include physical barriers, tumor microenvironment immunosuppression, heterogeneity, target specificity, limited reactive expansion vivo. Here, we developed CAR -T cells based on a novel CoupledCARTM technology to treat CoupledCAR significantly improved CAR-T vivo enhanced cells9 migration ability resistance immunosuppression by microenvironment, allowing infiltrate tissue sites increase anti-tumor activities.Specifically, engineered CoupledCAR-T with lentiviral vectors encoding an anti-GUCY2C (guanylate cyclase 2C) molecule. To verify safety efficacy for tumors, conducted several clinical trials different including two patients colorectal cancer. After infusion cells, these showed rapid killing cells. Spherically, observed that expanded infiltrated sites, demonstrating activities. Patient Profile: 1: Male, 55Y, Colon Adenocarcinoma. In May 2016, 8 cycles XELOX chemotherapy 1 dose radiotherapy were performed. Step “radical rectal resection terminal ileum double ileostomy” was surgery, gemcitabine performed 2 cycles. January 2018, relapse metastasis prostate left lung observed. Starting from March seven "Iritican + Retitrazepam Epitope Chemotherapy," one cycle Retitrazepam," implantation radioactive particles, three "Oxaliplatin Capecitabine" April 2019, 2: Female, 57Y, December 2014, DT46Gy/2Gy/23 2014 2015, single drug Xeloda taken orally. February laparoscopic radical cancer April, May, June, July mFOLFOX6 June CT metastasis. July, August irinotecan fluorouracil regimen Observations Results: One month after (M1), patient evaluated PR (Partial Response); most lesions reduced more than 50%, primary volume ~45%. M1, also PR; upper lobe tip posterior segment approximately 75%. The data demonstrated effectively expanded, killed We are recruiting further test Further, since our is platform technology, developing it other tumors using markers. Citation Format: Song Li, Chengfei Pu, Zhiyuan Cao, Cheng Lu, Hang Yang, Xi Huang, Xiaogang Shen, Xiuwen Wang, Zhao Wu, Lei Xiao. Novel coupledCARTMtechnology [abstract]. In: Proceedings Annual Meeting American Association Cancer Research 2020; 2020 Apr 27-28 Jun 22-24. Philadelphia (PA): AACR; Res 2020;80(16 Suppl):Abstract nr LB-380.