autologous dnTGF-BRII-armored anti-STEAP2 CAR T cells AZD0754

A preparation of autologous T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for the metalloreductase six-transmembrane epithelial antigen of prostate-2 (STEAP2; STAMP1) and the dominant negative (dn) form of transforming growth factor-beta (TGF-beta; TGFb) receptor 2 (dnTGF-BRII; dnTGFbR2), with potential immunomodulating and antineoplastic activities. Upon reintroduction into the patient, autologous dnTGF-BRII-armored anti-STEAP2 CAR T cells AZD0754 are directed to and induce selective toxicity in STEAP2-expressing tumor cells. STEAP2 is a cell surface antigen overexpressed in prostate cancer with limited expression in normal tissue. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the AZD0754 CAR T cells resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and plays a key role in tumor immune suppression.