PVRIG is an investigational monoclonal antibody being developed by Compugen to treat various types of cancer. A monoclonal antibody is a molecule that has the ability to bind with high specificity to a given target.
How PVRIG works
Certain immune cells, such as T-cells and natural killer (NK) cells, have proteins on their surface called immune checkpoints that help them distinguish between “self” and foreign or abnormal cells, like cancer cells. They work to protect against immune attacks on the body’s healthy cells and to eliminate dangerous cells.
Cancer cells can hijack this checkpoint system by expressing proteins on their surface that trick the immune system into “thinking” that they are normal, healthy cells. They do this by producing proteins that bind to the immune checkpoint receptors found on immune cells and deactivate them — essentially, turning this checkpoint off.
Immune checkpoint inhibitors are molecules that can stop this immune cell–cancer cell interaction. Essentially, these inhibitors work to take the “brakes” off immune cell receptors caused by the binding action of cancer cell proteins, allowing the immune system to recognize and kill tumor cells.
PVRIG is an immune checkpoint inhibitor that targets the immune checkpoint protein CGEN-15029. (CGEN-15029 was also discovered by Compugen, using a predictive software.)
Researchers have confirmed that CGEN-15029 is found on the surface of T-cells that infiltrate solid and hematologic cancers, or those relating to the blood system, including the bone marrow and lymph nodes. CGEN-15029’s binding partner, PVRL2, has been shown to be produced by many cancers, including breast, lung, and endometrial cancers.
PVRIG in trials
Preclinical studies of PVRIG, involving mice models, showed that it was able to inhibit the binding between CGEN-15029 and its binding partner, PVRL2, resulting in robust T-cell activation as well as reduced tumor growth. This study also discovered that administering PVRIG together with PD-1 inhibitors, an existing class of immune checkpoint blockers, resulted in a stronger T-cell function compared to alone.
This combination may benefit patients who failed to respond to PD-1 inhibitors, as PVRL2 was shown to be produced by a broader range of cancer tissues compared to the PD-1’s binding partner, PD-L1.
Preclinical data were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 in Chicago.
Compugen is planning to initiate Phase 1 clinical trial testing of PVRIG in humans in 2018.
Compugen has said it intends to file an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) by March 2018. A successful IND application grants pharmaceutical companies the permission to transport an investigational compound across state borders, for use by researchers in clinical trials.
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