Targeting ILDR2 with BAY 1905254: Unveiling a New Immune Checkpoint Inhibitor for Cancer Immunotherapy

The ILDR2 protein, part of the B7 family and highly conserved between humans and mice, has been linked to type 2 diabetes and tri-cellular junction formation, though its specific role remains undefined. It is found in various organs and notably in FRCs within the lymph nodes, which are crucial for immune cell recruitment and have immuno-regulatory characteristics.

Our research suggests ILDR2 may influence T cell activation and antigen-specific responses. We collaborated with Compugen to demonstrate that an ILDR2-Fc fusion protein can bind to activated T cells, inhibit cytokine release, and modulate immune responses in autoimmune disease models.

We developed BAY 1905254, an antibody against ILDR2, which selectively binds to it without cross-reactivity with related proteins. This antibody promotes T cell proliferation in a vaccination model and shows anti-tumor activity in mouse models, particularly in those with higher mutational loads. It also enhances the effects of anti-PD-L1 antibodies, chemotherapy, and tumor antigen immunization.

BAY 1905254 increases IFN-γ levels and CD45+ cell infiltration within tumors, with a notable impact on CD8α+ dendritic cells, which are vital for initiating CD8+ T cell responses. The antibody has shown promise as both a monotherapy and in combination with other treatments and is slated for first-in-man trials in 2018.

The study was presented at the American Association for Cancer Research Annual Meeting in 2018, highlighting the discovery and characterization of BAY 1905254 as a potential immune checkpoint inhibitor targeting ILDR2 for cancer immunotherapy.