Interleukin-15-armored GPC3-CAR T cells for patients with solid cancers

Interleukin-15 (IL15) enhances the antitumor properties of CAR T cells in preclinical solid tumor models but its effects on CAR T cells in humans are not known. Here, we report the first-in-human evaluation of IL15 co-expression in CAR T cells in two cohorts of a total of 24 patients with glypican-3 (GPC3) expressing solid neoplasms. In cohort 1, GPC3-CAR T cells were safe, no objective antitumor responses were detected. In cohort 2, co-expression of IL15 in GPC3-CAR T cells was associated with increased peak expansion in blood and measurable antitumor responses. Cytokine release syndrome was controlled with immunomodulation or with the inducible caspase 9 safety switch. Single cell transcriptomic analyses identified gene expression of tumor infiltrating CAR T cells associated with antitumor responses.