Express simultaneously targets TIGIT, PD-1 and PVRIG three immune checkpoints, and the combined therapy completes the first case of administration

▎ WuXi AppTec content team editor July 19, 2021, Compugen announced that in patients with advanced solid tumors, the Phase 1/2 dose escalation trial of its triple therapy combination has completed the first patient administration
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The triple combination uses Compugen's research anti-PVRIG antibody COM701, Bristol-Myers Squibb (BMS) PD-1 inhibitor Opdivo (nivolumab) and research anti-TIGIT antibody BMS-986207
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PVRIG is a new B7/CD28-like immune checkpoint protein, and PVRL2 is the ligand of PVRIG
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The results of preclinical experiments show that in patients who are resistant to targeted PD-1 immunotherapy, higher levels of PVRL2 in cancer cells may be a key biomarker
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Studies have shown that the combination of COM701 and anti-PD-1 antibodies can have a synergistic effect on stimulating T cells, and this type of combination has the potential to further enhance the immune response against tumors
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TIGIT is an inhibitory receptor protein mainly expressed on the surface of T cells and natural killer (NK) cells.
As an emerging immune checkpoint that has attracted much attention, no drugs targeting this target have been approved for marketing
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TIGIT can compete with CD226 (DNAM-1) to bind ligands CD155 and CD112.
DNAM-1 is a costimulatory molecule expressed on T cells and NK cells
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Previous studies have found that NK cells in most tumors express TIGIT
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And the role of TIGIT in tumor immunosuppression is similar to PD-1/PD-L1, and TIGIT inhibitors and PD-1/PD-L1 inhibitors can play a synergistic anti-tumor effect
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 In addition, Compugen has determined that PVRIG and TIGIT are key parallel and complementary inhibitory pathways in the DNAM pathway
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This means that to induce an effective anti-tumor response, certain patient groups may need to block both of them and the combination of PD-1 pathways
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▲Blocking PVRIG and TIGIT can produce a synergistic effect (picture source: Compugen's official website) COM701 is a humanized antibody that can bind to PVRIG with high affinity, thereby blocking its interaction with the ligand PVRL2
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The use of COM701 to inhibit PVRIG has been proven to effectively activate T cells and achieve reproducible enhancement effects
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BMS-986207 is a Bristol-Myers Squibb antibody drug under development that targets TIGIT.
It is currently in clinical trials as a single agent or in combination with PD-1 targeting drug Opdivo to treat patients with solid tumors
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Dr.
Anat Cohen-Dayag, President and CEO of Compugen, commented: “We believe that the future of immuno-oncology will be driven by combination therapies
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We believe that for certain tumors, blocking PVRIG and TIGIT at the same time can produce an anti-cancer immune response to them
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This experiment will test this hypothesis
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"Reference: [1] Compugen Doses First Patient in Phase 1/2 Triple Combination Cohort Expansion of COM701 with Opdivo® and Bristol Myers Squibb's Anti-TIGIT Antibody, BMS-986207.
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html Note: This article aims to introduce the progress of medical and health research and is not a recommendation for treatment plans
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