Unlocking the Potential of PTZ-201: Advancing TIGIT Antagonism for Cancer Immunotherapy

The abstract discusses the role of CD226 and TIGIT in immune regulation, akin to the CD28-CTLA4 system. Both molecules interact with PVR and PVRL2 ligands, but CD226 enhances T cell responses, whereas TIGIT inhibits them. TIGIT is prevalent in memory T cells and regulatory T cells (Tregs), and its activation modulates the activity of CD4+, CD8+ T cells, Tregs, and NK cells. Inhibiting TIGIT's ligand binding can stimulate immune responses in the tumor microenvironment, with TIGIT antagonists showing anti-tumor effects in mouse models.

PTZ-201, a human monoclonal IgG4 antibody by Potenza Therapeutics, is designed to block TIGIT's binding to its ligands. It exhibits high affinity binding to TIGIT and boosts IL-2 production in Jurkat cell assays. PTZ-201 also enhances IFNγ and TNF production in peripheral blood mononuclear cells and CD4+ T cells. In a cytomegalovirus-specific immune recall assay, PTZ-201 activates PBMCs and increases cytokine-producing CD4+ and CD8+ T cells, with a synergistic effect when combined with an anti-PD-1 antibody.

Tumor-infiltrating lymphocytes from various human tumors express high levels of TIGIT, often co-expressing PD-1. These findings encourage the advancement of PTZ-201 as a potential checkpoint inhibitor for cancer treatment. The study was presented at the American Association for Cancer Research Annual Meeting in 2018.