autologous anti-NY-ESO-1 TCR/dnTGF-BRII-expressing T cells GSK3845097

A preparation of human autologous T lymphocytes that are genetically modified to express a T-cell receptor (TCR) specific for the human cancer-testis antigen NY-ESO-1 and a dominant negative (dn) form of transforming growth factor-beta (TGF-beta; TGFb) receptor (dnTGF-BRII), with potential immunostimulating and antineoplastic activities. Upon leukapheresis, isolation, transduction, expansion ex vivo, and reintroduction into the patient, the autologous anti-NY-ESO-1 TCR/dnTGF-BRII-expressing T cells GSK3845097 recognize and bind to NY-ESO-1-overexpressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of NY-ESO-1-positive tumor cells. NY-ESO-1, a tumor-associated antigen (TAA), is found in normal testis and on the surface of various tumor cell types. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the GSK3845097 T cells resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and plays a key role in tumor immune suppression.