On October 27, 2020 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, reported the presentation of new research data further supporting PVRIG as a potentially promising target for cancer immunotherapy (Press release, Compugen, OCT 27, 2020, View Source [SID1234569169]). 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 are delivered in a presentation at the 2020 TIGIT Therapies Digital Summit today, October 27, 2020, at 11:00 AM EDT.

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"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 anti-tumor effects. 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," said Eran Ophir, Ph.D., Vice President of Research and Drug Discovery at Compugen. "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."

Anat Cohen-Dayag, Ph.D., President and CEO of Compugen, added, "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."

Key new findings presented by Dr. Ophir in the presentation titled, "Rationalizing Combination Strategies to Maximize Clinical Response as Novel ICI Therapies Emerge," include:

PVRIG is expressed on stem-like memory T cells (TSCM), the cells that give rise to differentiated cytotoxic effector T cells, mediating direct anti-tumor effects in the tumor microenvironment.
PVRL2 and PVR, the ligands for PVRIG and TIGIT, respectively, are expressed in both PD-L1low and PD-L1high tumor types.
PVRL2 has abundant expression across various dendritic cell (DC) types; PVRL2, PVR and PD-L1 are expressed by activated DCs which are associated with efficient T cell activation.
PVRL2 is expressed in tertiary lymphoid structures, structures in the tumor bed where local T cell priming occurs and which have been shown to be linked to positive response to immunotherapy.
Cumulatively, the data presented suggest that COM701 blockade could potentially mediate an interaction between DCs & 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.