ANTI-TIGIT – DOMVANALIMAB
TIGIT is a checkpoint found on immune cells in the tumor microenvironment that inhibits the immune system’s natural ability to detect and kill cancer cells. TIGIT is highly co-expressed with PD-1. Together, TIGIT and PD-1 act as dual brakes on anti-cancer immunity and require dual inhibition.
Left unchecked in the tumor microenvironment, TIGIT outcompetes DNAM-1 for binding to PVR, putting a brake on the immune system that leads to tumor progression.
A high level of tumor PVR expression is a poor prognostic factor in many tumor types and is correlated with poor response to PD-1 therapy alone.
When TIGIT is blocked, PVR is able to bind to DNAM-1 to activate the DNAM-1 pathway, accelerating the immune system to drive tumor cell death.
ABOUT DOMVANALIMAB
Domvanalimab (dom) is the most clinically advanced Fc-silent anti-TIGIT antibody in development. Domvanalimab is designed to turn TIGIT from a brake into an accelerator of anti-cancer immunity. By blocking the inhibitory brake of TIGIT, domvanalimab allows PVR to bind to DNAM-1, an accelerator on immune cells that causes tumor cell death.
Domvanalimab is engineered to be Fc-silent to avoid inducing antibody dependent cellular cytotoxicity (ADCC), which can lead to peripheral Treg depletion. Because Tregs are needed to maintain immune homeostasis, avoiding their depletion may prevent related autoimmune toxicities and immune-related side effects.
