ES009 is a potential best-in-class monoclonal antibody targeting LILRB2 designed to reprogram inhibitory myeloid cells to create an immune favorable tumor microenvironment (TME). In preclinical studies, ES009 demonstrated potent ligand blockade and effective reprogramming of tumor associated macrophages (TAMs) from M2 (pro-tumor) to M1 (anti-tumor) phenotype, leading to pro-inflammatory cytokine release from macrophages as well as T cell proliferation and activation.
Mechanism of Action
- LILRB2 is a critical inhibitory receptor expressed on myeloid cells (including monocytes, dendritic cells, macrophages and neutrophils), mediated by functional ligands such as HLA-G which are mainly expressed on tumor cells
- LILRB2 blocking promotes macrophage switch from pro-tumor M2 to anti-tumor M1 phenotype and activates pro-inflammatory response in the TME
- LILRB2-mediated immune suppression is regarded as one mechanism of anti-PD-(L)1 resistance
Key Differentiation
- Distinct binding epitope, multiple ligands blocker
- Superior blocking activity and more effective in reprograming TAMs from pro-tumor M2 to anti-tumor M1 phenotype
- Synergize with anti-PD-1 to reinvigorate T cells functionalities
