Abstract
PD-1/PD-L1 is an important signaling pathway in the adaptive immune system. The CD47/SIRPα signaling pathway is a crucial "do not eat me" signal for innate immunity. This study evaluated the anti-tumor mechanism of IMM2520 in vitro and in vivo. IMM2520 was generated using the "mab-trap" platform. IMM2520 showed high affinity to PD-L1 and relatively lower affinity to CD47, displaying preferential binding to PD-L1 on tumor cells. IMM2520 had the potent ability to inhibit the PD-1/PD-L1 and CD47/SIRPα signaling pathways and killed tumor cells through ADCC and ADCP. Importantly, IMM2520 did not bind to human red blood cells or induce erythrocyte agglutination. IMM2520 demonstrated a tendency to bind to CD47+/PD-L1+ tumor cells, reducing its binding to CD47 single-positive cells. In mouse transplantation models, compared with the first-generation CD47/PD-L1 BsAb (IMM2505), IMM2520 exhibited stronger and dose-dependent antitumor activity. These findings imply that IMM2520 may offer a novel therapeutic alternative for cancer patients.