Radioinducible CAR-T cells deliver TNF in preclinical tumor models

CAR-T therapy has shown limited efficacy in solid tumors, in part because of poor tumor infiltration and impaired effector function. In this study, researchers identified radiation-responsive genes in tumor-infiltrating T cells and used synthetic radioinducible promoters to engineer human CAR-T cells to release TNF after irradiation. TNF release did not require antigen engagement.

In human xenograft and murine tumor models, radioinducible TNF CAR-T cells combined with local irradiation produced greater tumor regression than either treatment alone or standard CAR-T cells combined with irradiation. The combination was associated with high intratumoral, but not systemic, TNF levels, alongside increased tumor necrosis and apoptosis, vascular disruption, and CAR-T cell infiltration.

The findings support a preclinical approach to spatially and temporally controlled cytokine delivery. They do not establish efficacy or safety in people: the supplied report gives no sample sizes or numerical effect estimates, and the evidence is from animal and xenograft models. Clinical relevance and potential toxicity require evaluation in human studies.