%0 Generic %A Wang, Yi %A Jiang, Hua %A Luo, Hong %A Sun, Yansha %A Shi, Bizhi %A Sun, Ruixin %A Li, Zonghai %D 2019 %T Data_Sheet_1_An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment.docx %U https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_An_IL-4_21_Inverted_Cytokine_Receptor_Improving_CAR-T_Cell_Potency_in_Immunosuppressive_Solid-Tumor_Microenvironment_docx/8961668 %R 10.3389/fimmu.2019.01691.s001 %2 https://frontiersin.figshare.com/ndownloader/files/16389674 %K CAR-T cells %K inverted cytokine receptors %K interleukin-4 %K interleukin-21 %K immunosuppressive tumor microenvironment %X

Incorporation of inverted cytokine receptor (ICR) such as interleukin (IL)-4 vs. IL-7 (4/7) ICR is one strategy to improve the antitumor activities of chimeric antigen receptor (CAR) modified T (CAR-T) cells facing immunosuppressive cytokines. Here we report a novel interleukin (IL)-4 vs. IL-21 ICR (4/21 ICR) that enhanced CAR-T cell potency in IL-4+ tumor milieu via a different working-mechanism from 4/7 ICR. Upon IL-4 stimulation, 4/21 ICR activated the STAT3 pathway and promoted Th17-like polarization and tumor-targeted cytotoxicity in CAR-T cells in vitro. Furthermore, 4/21 ICR-CAR T cells persisted and eradicated established IL-4+ tumors in vivo. Thus, 4/21 ICR is a promising clinical CAR-T cell therapeutics for solid tumors rich in IL-4.

%I Frontiers