New immune checkpoints are released, ILDR2 is expected to become a research hotspot
New immune checkpoints are released, ILDR2 is expected to become a research hotspot
February 11, 2018 Source: WuXi PharmaTech
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Compugen, based in Israel, is a biotech company that specializes in the development of new diagnostics and therapies using genomics. The company recently announced the discovery of an Ig-like domain-containing receptor 2 (Ig-like domain-containing receptor 2). , ILDR2) immunological checkpoint protein, which has the potential to become a new target for tumor immunotherapy, and can also be combined with the antibody Fc domain to form a fusion protein to treat autoimmune diseases. Two papers on this protein were published in the same issue of The Journal of Immunology in February 2018, describing ILDR2 as a novel B7 family of proteins that negatively regulate T cell responses, and ILDR2-Fc fusion proteins. A unique mechanism of action can improve autoimmune diseases.
The immune response has two sides. It needs to protect the body from foreign bodies and is resistant to its own antigen. Therefore, it is finely regulated by a series of molecules. The tolerance of the immune system to autoantigens is achieved by modulating T cell function. T cell activation requires two signals: the first is to recognize the antigen presented by the major histocompatibility complex (MHC) on antigen presenting cells (APC) to activate the T cell receptor (TCR); the second involves To co-stimulatory and co-inhibitory molecules belonging to the B7 family and tumor necrosis factor (TNF) family proteins expressed on APCs and T cells. The B7 family protein is a peripheral membrane protein found on activated APC that, when paired with CD28 or CD152 (CTLA-4) surface proteins on T cells, can produce a costimulatory signal or a co-suppression signal to enhance or decrease Signal activity between APC and T cells. Binding of B7 of APC to CTLA-4 of T cells can cause inhibition of T cell activity. Based on this understanding, the antibody drug ipilimumab (Yervoy) for the immune checkpoint CTLA-4 was approved by the US FDA in 2011, and its effect in many cancer treatments is gratifying. Since then, there have been more positive treatments for the B7 family member PD-L1 and its paired target PD-1 protein. Therefore, the B7 protein family is an attractive target for the development of novel therapies for disease.
In a recent paper, the researchers found that ILDR2 is a novel B7 family protein that is expressed in immune and inflammatory tissues and has potent T cell inhibitory activity. In a collagen-induced arthritis model, a fusion protein consisting of the extracellular domain of ILDR2 and an antibody Fc fragment binds to a corresponding binding partner on activated T cells, exhibiting beneficial effects and eliminating macrophages and via Cytokine-stimulated T cells produce auto-inflammatory cytokines and chemokines in autologous synovial-like co-cultures. These findings confirm that ILDR2 is a novel negative regulatory protein of T cells that has a potential role in the development of immune-related diseases, including autoimmunity and cancer.
In another paper, the researchers explored the properties of the ILDR2-Fc fusion protein and its role in the regulation of the immune system, demonstrating the short-term treatment with ILDR2-Fc, which can be used in relapsing-remitting experiments. Long-lasting beneficial effects are produced in a model of sexual autoimmune encephalomyelitis and non-obese (NOD) type 1 diabetes. ILDR2-Fc also promotes graft implantation in a mismatched bone marrow transplant model. The results show that ILDR2-Fc regulates immunity by regulating the balance of immune homeostasis and restoring immune tolerance, and these findings suggest the potential of ILDR2-Fc in the treatment of autoimmune diseases.
â–²Compugen's R&D pipeline (Source: Compugen)
In these understandings, Compugen will carry out further research and development. Antibody-based therapy targeting ILDR2 (Compugen named CGEN-15001T) has been licensed to Bayer for immuno Oncology development, but Compugen retains the full right to use ILDR2-Fc fusion protein in the field of autoimmune diseases. .
â–² Dr. Anat Cohen-Dayag, President and CEO of Compugen (Source: Compugen)
“The discovery, functional identification and potential therapeutic applications of ILDR2 can be published in prestigious peer-reviewed journals, which is an important affirmation of the scientific results of our research. Compugen first reported that ILDR2 is a new immune checkpoint and that it The potential therapeutic effects of autoimmune diseases and cancer immunotherapy have opened up the opportunity to develop first-in-class therapies in these areas," said Dr. Anat Cohen-Dayag, President and CEO of Compugen: "This It is the third new immune checkpoint we published after PVRIG and TIGIT. As we found the significance of the PVRIG/PVRL2 pathway in immuno-oncology and its potential clinical application, we have once again discovered a new approach, its role The mechanisms and broad therapeutic potential are supported by strong and diverse data."
Reference materials:
[1] Compugen Announces Publication of the Discovery of ILDR2 as a Novel Immune Checkpoint and its Use for the Treatment of Autoimmune Diseases in Two Back-to-Back Papers in The Journal of Immunology
[2] ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell Responses
[3] ILDR2-Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Immune Tolerance
[4] B7 family checkpoint regulators in immune regulation and disease.
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