Immunosuppressive tgf-b signal converter

Abstract

Embodiments of the disclosure concern cell therapy methods and compositions utilizing cells expressing at least a chimeric TGFβ receptor including the exodomain of a TGFβII receptor and an endodomain that is not from TGFβ receptor, thereby converting the negative signal of TGFβ for T cell proliferation into a T cell activation signal. In at least certain aspects, cells harboring the chimeric TGFβ receptor also harbor one or more chimeric antigen receptors.

What is claimed is: 
     
         1 . A chimeric TGFβ receptor polypeptide, wherein the receptor comprises an exodomain of TGFβ receptor and an endodomain of TLR4, wherein said polypeptide is comprised in a T cell. 
     
     
         2 . The polypeptide of  claim 1 , wherein the cell comprises a chimeric antigen receptor (CAR). 
     
     
         3 . The polypeptide of  claim 2 , wherein the CAR is specific for an antigen selected from the group consisting of PSCA, HER2, CD19, CD20, CD22, Kappa or light chain, CD30, CD33, CD123, CD38, ROR1, ErbB3/4, EGFR, EGFRvIII, EphA2, FAP, carcinoembryonic antigen, EGP2, EGP40, mesothelin, TAG72, PSMA, NKG2D ligands, B7-H6, IL-13 receptor α2, IL-11 receptor Ra, MUC1, MUC16, CA9, GD2, GD3, HMW-MAA, CD171, Lewis Y, G250/CAIX, HLA-AI MAGE A1, HLA-A2 NY-ESO-1, PSC1, folate receptor-α, CD44v7/8, 8H9, NCAM, VEGF receptors, 5T4, Fetal AchR, NKG2D ligands, CD44v6, TEM1, TEM8 and a combination thereof.