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Strategies harnessing Th17 functions in ACT: (a) Chimeric cytokine receptor formed by the extracellular domain of the IL-4R and the intracellular domain of the IL-21R, which dimerizes with the common γ chain. (b) Using ICOS or mutating the CD28 costimulatory domain (CD28*) polarizes CAR T cells towards a Th17 phenotype. (c) Engineering of TGF-β-producing cancer cells to secrete IL-6 skews T-cell polarization towards Th17. scFv: short-chain variable fragment.
