CD47 and PD-L1

Class

CD47/PD-L1 bispecific antibody (Nanjing Sanhome Pharmaceutical)

Pathway

Blocks CD47 "don't-eat-me" innate-immune evasion signal while inhibiting PD-L1 checkpoint on T cells

CD47 and PD-L1 are two distinct immune checkpoint molecules that tumors exploit to escape destruction. CD47 is a surface protein that binds SIRPα on macrophages, sending a "don't eat me" signal that blocks phagocytosis, the process by which these innate immune cells engulf abnormal or damaged cells. PD-L1 acts on the adaptive immune system, binding PD-1 on T cells to dampen their cytotoxic activity. Many cancers overexpress both proteins, simultaneously evading innate clearance and T-cell killing. A bispecific antibody engaging both targets at once aims to restore two complementary arms of anti-tumor immunity in a single molecule: unleashing macrophages to engulf tumor cells while reactivating exhausted T cells to kill them directly. This dual approach also offers a targeting advantage: because CD47 is expressed broadly on healthy cells (including red blood cells), agents that bind CD47 alone can cause unwanted destruction of normal tissue. Linking CD47 blockade to PD-L1 binding can help concentrate the antibody's activity on tumor cells that co-express both markers, potentially sparing normal cells that express CD47 but not PD-L1. This mechanism is broadly relevant across solid tumors and hematologic malignancies where immune evasion through both innate and adaptive checkpoints contributes to disease persistence.