Targeting PVRIG with COM701: Advancing Cancer Immunotherapy

The study explores the role of PVRIG, a newly identified member of the B7/CD28 family, as a potential target for cancer therapy. Computational algorithms were used to discover PVRIG, which is expressed by T and NK cells within the tumor microenvironment and interacts with PVRL2. The research focused on the expression pattern, functional characterization, and anti-tumor activity of blocking antibodies against PVRIG, as well as the creation and analysis of PVRIG knockout (KO) mice.

Through phage display and hybridoma platforms, antibodies were developed and screened for their capacity to boost T-cell activity in vitro. A lead antibody, COM701, was selected for its high affinity and ability to block the PVRIG-PVRL2 interaction, enhancing the activation of both primary and tumor-derived immune cells. COM701 also showed significant improvement in T cell function when used in combination with PD1 or TIGIT antibody blockade.

PVRIG KO mice were developed to study the phenotypic and immune response differences between PVRIG null and wild-type (WT) T cells. The KO mice exhibited slower tumor growth and enhanced anti-cancer immunity compared to WT mice. A surrogate antibody that blocks the PVRIG-PVRL2 interaction was found to inhibit the growth of colon carcinoma and melanoma in combination with an anti-PDL1 antibody.

The study concludes that PVRIG is a novel T cell immune checkpoint with potential for therapeutic targeting. The antibody COM701, currently in preclinical development, demonstrates the potential for PVRIG blockade to be effectively combined with other checkpoint inhibitors to enhance anti-tumor immunity. This suggests that targeting PVRIG could be a valuable addition to current cancer treatment strategies.