Reversing the effects of the tumor microenvironment using chimeric cytokine receptors

摘要

Disclosed are compositions and methods related to rendering ineffective Th1 T cells resistant to the inhibitory cytokine milieu present in a cancer microenvironment. Tumor-specific T cells are modified to employ a chimeric receptor that binds inhibitory/suppressive cytokines and converts their intracellular consequences to a Th1 immunostimulaotyr/activating signal. The T cells employ a chimeric antigen receptor having exodomains for IL10, IL13 and/or IL4 fused with the signal transducing endodomains for IL2 and/or IL7.