PM1003

PM1003 is a bispecific antibody designed to target both programmed death-ligand 1 (PD-L1) and 4-1BB (CD137), developed for the treatment of advanced malignant solid tumors. Its mechanism of action involves simultaneous blockade of PD-L1, thereby inhibiting immune checkpoint signaling, and agonistic activation of 4-1BB, a co-stimulatory receptor on T cells. This dual targeting is achieved through cross-bridging—PM1003 binds PD-L1 on tumor cells and 4-1BB on effector immune cells—resulting in enhanced anti-tumor immune responses with minimized off-target toxicity. The antibody incorporates LALA mutations in its Fc region to reduce Fc receptor binding and further limit adverse effects. Preclinical studies demonstrated potent activation of 4-1BB only in the presence of PD-L1, with no evidence for PD-L1-independent activation. Early clinical trials have shown that PM1003 is well-tolerated up to doses of at least 6 mg/kg and has exhibited preliminary anti-tumor activity in heavily pretreated patients[6][2][5][1]. The drug was initially developed by Biotheus.