ILT2 and ILT4 (immunoglobulin-like transcript receptors 2 and 4)

Class

Dual anti-ILT2/ILT4 humanized monoclonal antibody (myeloid immune checkpoint inhibitor)

Pathway

Blocks HLA-G/ILT2 and ILT4-mediated suppression of myeloid cells and lymphocytes

ILT2 and ILT4 are inhibitory receptors—members of the immunoglobulin-like transcript family, also called LILRB1 and LILRB2—found on myeloid cells such as macrophages and dendritic cells, and, in the case of ILT2, also on natural killer cells and some T and B lymphocytes. They recognize class I human leukocyte antigen (HLA) molecules, most notably HLA-G, a non-classical HLA variant that tumors often overexpress to dampen immune attack. Engagement of ILT2/ILT4 delivers an inhibitory signal that suppresses antigen presentation, phagocytosis, and cytotoxic activity, contributing to an immunosuppressive tumor microenvironment. Because ILT4 is largely restricted to myeloid cells while ILT2 extends to lymphocytes, an antibody blocking both receptors can relieve suppression across the innate and adaptive arms of the immune system simultaneously, addressing myeloid-driven immune evasion that lymphocyte-focused checkpoint inhibitors do not target. This mechanism is of broad interest in oncology, particularly in cancers where tumor-associated macrophages and HLA-G expression are prominent features of immune escape, and as a complement to existing T-cell checkpoint blockade strategies.