Novel CoupledCAR technology for treating colorectal cancer.

Abstract

e15035 Background: Conventional CAR-T cell therapy has thus far shown weak cell expansion in solid tumor patients and achieved little or no therapeutic responses. Methods: We developed CAR T cells based on a novel CoupledCAR technology to treat solid tumors. We engineered CoupledCAR-T cells with lentiviral vectors encoding an anti- colorectal cancer specific protein CAR molecule, and anti- colorectal cancer specific protein (CRCSP) CAR-T cells showed anti-tumor activities in vitro and in vivo experiments. Further, we conducted several clinical trials for various solid tumors, including two patients with colorectal cancer. After the infusion of CoupledCAR T cells, these two patients showed rapid expansion of CoupledCAR T cells and the killing of tumor cells. Specifically, we observed that CoupledCAR T cells expanded significantly in the patients and infiltrated tumor tissue sites. Results: Both patients achieved PR (Partial Response). Patient Profile: Patient 1: Male, 55Y, Colon Adenocarcinoma. In May 2016, 8 cycles of XELOX chemotherapy and 1 dose of radiotherapy were performed. In Step 2016, “radical rectal resection and terminal ileum double ileostomy” was performed. After surgery, gemcitabine chemotherapy was performed for 2 cycles. In January 2018, relapse and metastasis of prostate and left lung were observed. In April 2019, relapse and metastasis were observed. Patient 2: Female, 57Y, Colon Adenocarcinoma. In December 2014, DT46Gy/2Gy/23 radiotherapy was performed. In December 2014 and January 2015, the single drug chemotherapy of Xeloda was taken orally. In February 2015, laparoscopic radical resection of rectal cancer was performed. In April, May, June, and July 2015, mFOLFOX6 chemotherapy was performed. In June 2019, CT showed tumor metastasis. Observations and Results: Patient 1: One month after infusion (M1), the patient was evaluated as PR; most of the target lesions were significantly reduced by more than 50%, and the primary tumor volume was reduced by ~45%. Patient 2: M1, the patient was also evaluated as PR; the tumor in the left upper lobe tip posterior segment was reduced by approximately 75%. Conclusions: The clinical data demonstrated that CoupledCAR-T cells effectively expanded, infiltrated tumor tissue sites, and kill tumor cells in patients with colorectal cancer. We are recruiting more colorectal cancer patients to further test the safety and efficacy of anti-CRCSP CoupledCAR T cells. Further, since our CoupledCAR technology is a platform technology, we are developing it to treat other solid tumors using different target markers.