Meng-Yin Lin, Eunwoo Nam, Ryan M Shih, Amanda Shafer, Amber Bouren, Melanie Ayala Ceja, Caitlin Harris, Mobina Khericha, Kenny H Vo, Minsoo Kim, Chi-Hong Tseng, Yvonne Y Chen
Cytokine release syndrome (CRS) is a frequently observed side effect of chimeric antigen receptor (CAR)-T cell therapy. Here, we report self-regulating T cells that reduce CRS severity by secreting inhibitors of cytokines associated with CRS. With a humanized NSG-SGM3 mouse model, we show reduced CRS-related toxicity in mice treated with CAR-T cells secreting tocilizumab-derived single-chain variable fragment (Toci), yielding a safety profile superior to that of single-dose systemic tocilizumab administration...
June 3, 2024: Journal of Experimental Medicine