Novel Methods of MHC-I - LILRB Checkpoint Inhibition

The technology encompasses antibodies and methods that may overcome the shortcomings of commercial checkpoint inhibitors (CPIs). Scientists at NIAID have identified MHC-I specific antibodies that selectively inhibit interactions with inhibitory leukocyte immunoglobin-like receptors (LILRs) but not T-cell receptors. Administration of the antibodies increased proliferation and activation of both innate and adaptive immune system cells, and lead to anti-tumor and anti-viral activity in an array of relevant mouse models of disease.

Immune CPIs that target PD-1/PD-L1, CTLA-4 and other well-known molecules can provide significant clinical benefit as part of a mono or combination immunotherapy regimen. However, many patients do not respond to treatment, leading to an ongoing search for novel checkpoint targets. One attractive family of targets are the inhibitory Leukocyte Immunoglobin-like receptors (LILRB1-5). LILRB1, LILRB2, and LILRB5 can inhibit immune cell function by binding to many MHC-I subtypes. However, LILRB1/2/5 expression is variable and the three members cannot be targeted by any single blocking anti-LILB antibody, possibly limiting the efficacy of targeting LILRBs. NIAID scientists have circumvented these issues by identifying antibodies that can inhibit LILRB function by binding to MHC-I without interfering with T-cell receptor engagement.

To date, the MHC-I specific antibodies have been shown to induce activation and proliferation of human T cells and NK cells in xenogeneic models using NSG mice.

This technology is available for licensing for commercial development in accordance with 35 U.S.C. § 209 and 37 CFR Part 404, as well as for further development and evaluation under a research collaboration.