Tumors exploit checkpoint inhibitory receptors, e.g. by expressing inhibitory LILRB receptors to suppress the immune system. Therefore, LILRB receptors are important targets in cancer immunotherapy. In addition, other receptors beyond LILRB receptors that inhibit myeloid cell activation create an opportunity to utilize multi-specific antibodies that target multiple distinct receptors on immune cells and tumor cells to not only activate T cells, B cells and NK cells but also macrophages and macrophage derived cells. One of the key pathways to suppress activation of macrophages is the CD47 receptor and SIRP-a ligand. CD47 is highly expressed on tumor cells and binds to its ligand SIRP-a which is expressed on macrophages. This interaction creates an immunosuppressive tumor microenvironment and prevents the macrophages from being activated and destroying the tumor cells. The immuno-oncology pipeline includes multi-specific molecules that target not only the LILRB receptors but also the CD47 pathway. In addition, ImmunOs is currently conducting clinical trials in solid tumors with an HLA-Fc fusion protein that targets LILRB1, LILRB2 and KIR3DL1 inhibitory receptors.
The diagram below illustrates which immune cell types express the LILRB receptors to create an immunosuppressive environment characteristic of a cold tumor. In addition, LILRB receptors can be expressed on tumor cells and their expression correlates with a poor prognosis in specific tumor types.
