ES019：Anti-SIRPα/PD-L1 BiME® Molecule to Kill Solid Tumors
Tumor-associated macrophages are major component of immune cells in the tumor micro-environment (TME) that express an array of effector molecules leading to the inhibition of anti-tumor immune responses. SIRPα is a myeloid-lineage inhibitory receptor primarily expressed on phagocytic macrophages and DCs, which inhibits phagocytosis through engagement of its ligand CD47 expressed on tumors and normal tissues.
Based on our Bispecific Macrophage Engager (BiME®) technology, we have developed a PD-L1/SIRPα bispecific antibody that is capable of reactivating macrophages and T cells to kill cancer cells. The anti-PDL1/SIRPα bispecific antibody ES019, designed for tumor cell and immune cell dual targeting, demonstrated significantly enhanced tumor therapeutic efficacy versus combo or monotherapies.
Mechanism of Action
- Tumor cell-macrophage engagement
- Blockade of “don’t eat me” signal by anti-SIRPα
- Activate “eat me” signaling via Fc engagement
- PD-L1 dependent specific phagocytosis of tumor cells
- Activated macrophages could present tumor antigens to cytotoxic T cells, which could be further activated by checkpoint PD1/PD-L1 blockade
Key Differentiation
- Achieve better in vivo anti-tumor efficacy in animal models than combinational study of SIRPa and PD-L1 antibody
- Activate T cells without induction of phagocytosis of T cells
- Shows favorable pharmacokinetics in mouse model
