Targeting PVRIG in cancer immunotherapy

Expression data suggest potential of PVRIG inhibition to enhance T cell priming and infiltration into both inflamed and less inflamed tumors

November 25, 2020
Jeffrey Bouley

HOLON, Israel—Compugen Ltd. recently presented new research data further supporting the PVRIG protein coding gene as a potentially promising target for cancer immunotherapy. These data suggest that PVRIG inhibition may enhance T cell priming and infiltration into tumors and provide further evidence supporting the potential advantages of targeting PVRIG—alone and in combination with TIGIT and PD-1 inhibitors—in tumors for which current checkpoint blockers have not proven successful.

The new findings were delivered in a presentation at the 2020 TIGIT Therapies Digital Summit in late October.

“There is a growing appreciation for the potential role of stem-like memory T cells—known as TSCM—in cancer biology, as these cells can self-renew and differentiate into effector cells that mediate direct antitumor effects,” said Dr. Eran Ophir, vice president of research and drug discovery at Compugen. “While recent evidence suggests that TSCM cells express TIGIT and PD-1, our work now shows that they also express PVRIG. Furthermore, our data show that PVRIG’s ligand, PVRL2, is expressed in both dendritic cells and tertiary lymphoid structures, as well as in PD-L1low less inflamed tumors.

“These new data suggest that PVRIG may be involved in the inhibition of T cell proliferation, activation and infiltration into tumors and that its blockade by COM701, our first-in-class PVRIG inhibitor, may enhance T cell proliferation and infiltration into tumors through the modulation of these important cell populations, even in tumors in which current checkpoint blockers have not proven successful.”

Added Dr. Anat Cohen-Dayag, president and CEO of Compugen: “We are excited to share this new data showing that PVRIG and PVRL2 are expressed in three cell types: TSCM cells, dendritic cells and tertiary lymphoid structures, all of which have been shown to be important in clinical response to checkpoint inhibitors. These data reinforce our view that PVRIG plays a significant role within the DNAM axis in triggering an immune response in the tumor microenvironment.

“As such, targeting the PVRIG pathway has the potential to provide new treatment options, as monotherapy or in combination with other immune checkpoints, for both inflamed and less inflamed tumors. Additionally, the co-expression of PVRIG, TIGIT and PD-1 on TSCM cells and their ligands on activated dendritic cells further substantiates our hypothesis that the simultaneous triple blockade of these pathways has the potential to expand the reach of cancer immunotherapies to new patient populations and cancer indications currently unresponsive or refractory to existing treatments.”

Cumulatively, the data presented suggest that COM701 blockade could potentially mediate an interaction between dendritic cells TSCM cells in the tumor bed and lymphoid organs. This potential mechanism could lead to increase T cell priming and infiltration into less inflamed tumors.

Subscribe to Newsletter
Subscribe to our eNewsletters

Stay connected with all the latest DDN news!

Latest Issue's Magazine Cover

Latest Issue  

• Volume 17 • Issue 3 • March 2021

March 2021

March 2021 issue