PVRIG and TIGIT combined with PD-1 for the treatment of solid tumors, completed the first patient drug delivery

Recent popular reports from Yimaike★Global leader! Bangyao Biological Announces Preliminary Data from Multi-center Clinical Research on Gene Therapy of ThalassemiaYimai Meng broke the news ★Two South Korean companies merged: owns the CAR-NK favored by Merck and 15-year-old T-cell productYi Meng broke the news by clicking on the picture, Sign up now July 21, 2021/MedClub News/--Recently, Compugen announced that in patients with advanced solid tumors, its PVRIG antibody COM701 and BMS's research TIGIT antibody BMS-986207 and PD-1 inhibitor Opdivo's triple therapy combination has been administered to the first patient in the Phase 1/2 dose escalation trial
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This study aims to evaluate the safety, tolerability and preliminary anti-tumor activity of blocking the three immune checkpoint pathways PVRIG, TIGIT and PD-1 at the same time, and to examine the simultaneous blocking of PVRIG and TIGIT in certain tumor types to produce Or the hypothesis of enhancing the anti-tumor immune response
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Compugen said it expects to report preliminary data from the study’s triple-combined dose escalation unit in the fourth quarter of this year
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COM701 is a humanized antibody that can bind to PVRIG with high affinity
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PVRIG is a new B7/CD28-like immune checkpoint protein, which is an important signaling pathway for T and NK cell functions
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PVRIG is located on the surface of T and NK cells
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Studies exploring the PVRIG pathway have shown that when combined with its ligand PVRL2, PVRIG inhibits the activity of T and NK cells
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Compugen’s team found through calculations in 2009 that TIGIT works in parallel with and complements PVRIG on the DNAM axis (the central node where multiple receptors and ligands are connected to form a family).
When TIGIT binds to its ligand PVR, it will also The activity of T and NK cells is inhibited
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▲Dnam axis diagram (picture source: Compugen) TIGIT is an emerging inhibitory receptor protein, which is highly expressed on the surface of natural killer (NK) cells.
At present, studies have confirmed that immunotherapy based on TIGIT can reverse the function of NK cells Depletion, enhance the anti-tumor immune response mediated by NK cells, and effectively inhibit the growth of mouse tumors
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Recommended reading: the first in China! Cinda Bio-assisted TIGIT monoclonal antibody IBI939 approved for clinical use.
Although PVRIG and TIGIT are complementary and part of the same biological axis, studies have shown that they are actually different
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PVRIG and TIGIT bind different ligands (PVRL2 and PVR, respectively), they are expressed on different immune cell types, and their ligands have different expression patterns
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The data shows that PVRIG is expressed in stem cell-like memory T cells (T-SCM), PVRL2 is expressed in dendritic cells and tertiary lymphoid structures, and PD-L1 is expressed in tumors with low inflammation
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T-SCM cells, dendritic cells, and tertiary lymphoid structures have all been shown to be important in the clinical response to checkpoint inhibitors
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Extensive preclinical data and preliminary clinical results show that it can be the main inhibitor in tumor types with high expression of PVRIG, such as breast cancer, endometrial cancer and ovarian cancer.
Therefore, blocking PVRIG through COM701 may trigger a meaningful and long-lasting anti-tumor immune response
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Other preclinical data indicate that after combined treatment with COM701 and TIGIT inhibitors, there is a synergistic effect on T cell activation
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In addition to the potential biological role of the DNAM axis, the researchers also found that there is a cross path between the TIGIT/PVRIG pathway and the inhibitory PD-1 on the DNAM axis
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▲Triple pathway hypothesis: PVRIG, TIGIT, PD-1 (picture source: Compugen) According to Compugen's 2020 AACR report, the combination of PVRIG antibody or gene knockout mouse and PD-L1 antibody is better than PD in MC38 and CT26 models -L1 antibody single drug has better therapeutic effect; and the tumor growth control in double knockout mice of PVRIG and TIGIT is further improved compared with single knockout mice
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Further studies have shown that using PVRIG/TIGIT/PD-1 antibodies to activate TILs in different types of patient tumors in vitro, we can see the combined use of PVRIG and TIGIT antibodies, and the synergistic effect of their combined use with PD-1 antibodies
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▲The individual or combined effects of antibody blocking or gene knockout PVRIG/TIGIT/PD-1 in various tumor models (picture source: reference 3) PVRIG/TIGIT/PD-1 antibody triad combination still needs more It is verified in the system and model, but the existing data supports this strategy to a certain extent
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"As a leader in the DNAM axis field and a biological company evaluating the potential synergy of PVRIG, TIGIT and PD-1 triple therapy in the clinic, we will continue to move forward
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" said Dr.
Anat Cohen-Dayag, President and CEO of Compugen, "We believe that the future of immuno-oncology will be driven by combination therapies.
The three-channel hypothesis of this study is an important part of our overall strategy and an important step for Compugen to examine the potential benefits of this unique combination of immunotherapy in a wider range of patients
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"▲Dr.
Anat Cohen-Dayag, President and CEO of Compugen (Image source: Compugen official website) Compugen is a clinical stage drug discovery and development company that uses a widely applicable predictive computational discovery platform to identify new drug targets and new drugs Biological approaches, and the development of treatment methods in the field of cancer immunotherapy
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Recognizing the potential of immuno-oncology to change the prospect of cancer treatment, Compugen focuses on the discovery of new drug targets to expand the scope of cancer immunotherapy to new patient groups
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▲ Compugen's research pipeline (picture source: Compugen official website) Reference materials: 1.
https:// cohort-expansion-of-com701-with-opdivo-and-bristol-myers-squibbs-anti-tigit-antibody-bms-986207-301336286.
html 2.
https://cgen.
com/pipeline/com701-pvrig/3.
https://cgen.
com/wp-content/uploads/Abstract-9757-AACR-2020-Oral-Virtual-COM701-Phase-1-Dose-Escalation-Arms-A-and-B-FINAL-27-04- 2020.
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