Enhanced anti-tumor efficacy of IL-7/CCL19-producing human CAR-T cells in orthotopic and patient-derived xenograft tumor models

Chimeric antigen receptor (CAR)-T cell therapy has impressive efficacy in hematological malignancies, but its application solid tumors remains a challenge. Multiple hurdles associated with the biological and immunological features of currently limit CAR-T cells treatment tumors. Using syngeneic mouse models, we recently reported that engineered to concomitantly produce interleukin (IL)-7 chemokine (C–C motif) ligand 19 (CCL19)-induced potent anti-tumor against through an improved ability migration proliferation even immunosuppressive tumor microenvironment. In this study, for preclinical evaluation preceding clinical application, further explored potential IL-7/CCL19-producing human using models mimic Human anti-mesothelin producing IL-7/CCL19 achieved complete eradication orthotopic pre-established malignant mesothelioma prevented relapse downregulated expression. Moreover, mice patient-derived xenograft mesothelin-positive pancreatic cancers exhibited significant inhibition growth prolonged survival following cells, compared conventional cells. Transfer resulted increase not only also non-CAR-T within tissues expression exhaustion markers, including PD-1 TIGIT, on T Taken together, our current study elucidated exceptional their patients