Bing Chen1, Min Zhou1, Hai Zhang2, Chen Wang3, Xiaocui Hu3, Bo Wang4, Enxiu Wang3. 1. Department of Hematology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, PR China. 2. Department of Research and Development, Nanjing Aide Institute of Immunotherapy, Nanjing 211808, PR China. 3. Nanjing CART Medical Technology Co., Ltd, Nanjing 210032, PR China. 4. Department of Medical Oncology, The Seventh Affilliated Hospital, Sun Yat-Sen Universityl, Shenzhen 518107, PR China.
Abstract
Aim: Chimeric antigen receptor-engineered T (CAR-T) cells have gained huge success in treating hematological malignancies, yet the CD3ζ-based CAR-T therapies have not shown comparable clinical benefits in solid tumors. We designed an alternative chimeric immunoreceptor in which a single-chain variable fragment was fused to the transmembrane-cytoplasmic domains of triggering receptor expressed on myeloid (TREM1), which may show potent antitumor activity. Methods: To generate TREM1/DNAX activation protein of 12 kDa (Dap12)-based CAR-T cells, TREM1 along with DAP12 was transduced into T cells. Results: TREM1/Dap12-based CAR-T cells showed more lysis in vitro and a similar antitumor effect in mouse models compared with CD19BBζ CAR-T cells. Conclusion: In this study, we designed a TREM1/Dap12-based CAR, which was not reported previously and demonstrated that TREM1/Dap12-based CAR-T cells had potent antitumor activity in vitro and in vivo.
Aim: Chimeric antigen receptor-engineered T (CAR-T) cells have gained huge success in treating hematological malignancies, yet the CD3ζ-based CAR-T therapies have not shown comparable clinical benefits in solid tumors. We designed an alternative chimeric immunoreceptor in which a single-chain variable fragment was fused to the transmembrane-cytoplasmic domains of triggering receptor expressed on myeloid (TREM1), which may show potent antitumor activity. Methods: To generate TREM1/DNAX activation protein of 12 kDa (Dap12)-based CAR-T cells, TREM1 along with DAP12 was transduced into T cells. Results:TREM1/Dap12-based CAR-T cells showed more lysis in vitro and a similar antitumor effect in mouse models compared with CD19BBζ CAR-T cells. Conclusion: In this study, we designed a TREM1/Dap12-based CAR, which was not reported previously and demonstrated that TREM1/Dap12-based CAR-T cells had potent antitumor activity in vitro and in vivo.
Authors: Kun Chen; Shuhang Wang; Dan Qi; Peiwen Ma; Yuan Fang; Ning Jiang; Erxi Wu; Ning Li Journal: Front Immunol Date: 2022-07-18 Impact factor: 8.786