Cancer immunotherapy has transformed treatment for some patients, but many tumors still do not respond well to current options, including checkpoint inhibitors. Researchers at NIAID’s Laboratory of Immune System Biology (LISB) have developed new antibodies designed to help the immune system fight tumors. These lab-made antibodies, called pan-anti-HLA monoclonal antibodies, block signals that can limit immune cell activity.

       These signals are part of a pathway that regulates immune responses. In this pathway, inhibitory receptors in the leukocyte immunoglobulin-like receptor (LILR) family, found on many immune cells like natural killer (NK) cells and T cells, act like a brake when they interact with molecules called MHC-I. The antibodies are designed to block this interaction and release that brake. Earlier studies showed that antibodies targeting this interaction could activate both innate immunity, the body’s first line of defense, and adaptive immunity, the part of the immune system that builds more targeted responses and immune memory.

       The new pan anti-HLA antibodies 3C10 and 15B1 block LILR interactions by binding to a different site on MHC-I than previously developed antibodies DX17 and W6/32. They also bind more than 50 times better and activate human NK and T cells for tumor control. To support development of next-generation checkpoint therapies, researchers will further evaluate the 3C10 and 15B1 antibodies in animal and tissue-based models.