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bioRxiv · 10.1101/2021.06.18.449074

IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors

chi, t.·zou, y.
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Abstract

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 HER2-specific CAR T cells targeting breast cancer cells did not affect proliferation or differentiation of the CAR T cells in the absence of tumors, but markedly enhanced killing of the cancer cells in vitro and in a xenograft model. 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.

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chi, t., zou, y.. 2021-06-19. IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors. https://doi.org/10.1101/2021.06.18.449074

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