IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors

Chimeric antigen receptor (CAR) T cell therapy has been successful in treating hematological malignancy, but solid tumors remain refractory. Here, we demonstrated that knocking out transcription factor IKZF3 in HER2specific CAR T cells targeting breast cancer cells did not affect CAR expression or CAR T cell differentiation, but markedly enhanced killing of the cancer cells in vitro and in a xenograft model, which was associated with increased T cell activation and proliferation. Furthermore, IKZF3 KO had similar effects on the CD133-specific CAR T cells targeting glioblastoma cells. AlphaLISA and RNA-seq analyses indicate that IKZF3 KO increased the expression of genes involved in cytokine signaling, chemotaxis and cytotoxicity. Our results suggest a general strategy for enhancing CAR T efficacy on solid tumors.

Automated summary

Knocking out transcription factor IKZF3 enhances the killing effect of CAR T cells on solid tumors, leading to increased T cell activation and proliferation. The strategy of IKZF3 KO may improve the efficacy of CAR T cells in treating solid tumors.