Fu and Lei et al. observed that exosomes derived from EGFR and HER2-targeted CAR T cells expressed surface CAR, contained perforin and granzyme B, specifically lysed target antigen-expressing cancer cells in vitro, and delayed tumor growth in a dose-dependent manner in EGFR or HER-2-positive mouse and human xenograft models. Exosomes did not induce cytokine release syndrome or other toxicities associated with CAR T cells. CAR exosomes did not contain PD-1, and codelivery of recombinant PD-L1 with CAR T cells, but not CAR T exosomes, blocked cytotoxicity in vitro and antitumor efficacy in vivo.
Contributed by Alex Najibi
Genetically engineered T cells expressing a chimeric antigen receptor (CAR) are rapidly emerging a promising new treatment for haematological and non-haematological malignancies. CAR-T therapy can induce rapid and durable clinical responses but is associated with unique acute toxicities. Moreover, CAR-T cells are vulnerable to immunosuppressive mechanisms. Here, we report that CAR-T cells release extracellular vesicles, mostly in the form of exosomes that carry CAR on their surface. The CAR-containing exosomes express a high level of cytotoxic molecules and inhibit tumour growth. Compared with CAR-T cells, CAR exosomes do not express Programmed cell Death protein 1 (PD1), and their antitumour effect cannot be weakened by recombinant PD-L1 treatment. In a preclinical in vivo model of cytokine release syndrome, the administration of CAR exosomes is relatively safe compared with CAR-T therapy. This study supports the use of exosomes as biomimetic nanovesicles that may be useful in future therapeutic approaches against tumours.
Author Info: (1) Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, 200011, Shanghai, China. (2) Department of Bio
Author Info: (1) Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, 200011, Shanghai, China. (2) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. (3) Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. (4) Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. (5) Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. (6) Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. (7) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. (8) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. (9) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. (10) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. (11) Pharchoice Therapeutics Inc., 201406, Shanghai, China. (12) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. (13) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. (14) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. (15) Department of Biophysics, College of Basic Medical Sciences, Second Military Medical University, 200433, Shanghai, China. hus@smmu.edu.cn. Team SMMU-China of International Genetically Engineered Machine (iGEM) Competitions, Department of Biophysics, Second Military Medical University, 200433, Shanghai, China. hus@smmu.edu.cn.
