autologous dnTGF-BRII-armored anti-GPC3 CAR T cells AZD5851

A preparation of autologous T lymphocytes that have been genetically modified to express a chimeric antigen receptor (CAR) specific for glypican-3 (GPC3) 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-GPC3 CAR T cells AZD5851 are directed to and induce selective toxicity in GPC3-expressing tumor cells. GPC3, a heparan sulfate proteoglycan and a member of the glypican family, is overexpressed on certain tumor cell types while minimally expressed on normal, healthy cells; GPC3 plays an important role in cellular proliferation and differentiation. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the AZD5851 T cells resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and plays a key role in tumor immune suppression.