Allogeneic Anti-CD70 CAR/dnTGF-BRII-expressing Gamma Delta T-cells ADI-270
allogeneic anti-cd70 car/dntgf-brii-expressing gamma delta t-cells adi-270
A preparation of allogeneic Vdelta1 gamma delta T-lymphocytes engineered to express a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) human cluster of differentiation 70 (CD70) and a dominant negative (dn) form of transforming growth factor-beta (TGF-beta; TGFb) receptor II (dnTGF-BRII), with potential immunostimulating and antineoplastic activities. Upon administration, allogeneic anti-CD70 CAR/dnTGF-BRII-expressing gamma delta T-cells ADI-270 recognize and bind to CD70-expressing tumor cells. This may result in a specific cytotoxic T-lymphocyte (CTL)-mediated killing of CD70-positive tumor cells. CD70, a type II transmembrane glycoprotein and member of the tumor necrosis factor (TNF) family, is found on the surfaces of various types of cancer cells. The inclusion of dnTGF-BRII blocks the signaling of the immunosuppressive cytokine TGFb in the tumor microenvironment (TME) and makes the ADI-270 T-cells resistant to TGFb. TGFb negatively regulates T-cell proliferation and activation and plays a key role in tumor immune suppression. Gamma delta T-lymphocytes play a key role in the activation of the immune system and do not require major histocompatibility complex (MHC)-mediated antigen presentation to exert their cytotoxic effect.