anti-TROP-2 antibody-drug conjugate DB-1305

An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the tumor-associated antigen (TAA) trophoblast cell surface protein 2 (trophoblast antigen 2; calcium signal transducer 2; TROP2; TROP-2; TACSTD2; GA733-1; M1S1) covalently linked, via a cleavable linker containing maleimide tetrapeptide, to the topoisomerase-1 inhibitor P1021, with potential antineoplastic activity. Upon administration of the anti-TROP-2 ADC DB-1305, the anti-TROP-2 antibody targets and binds to TROP-2 expressed on tumor cells. Upon binding and internalization, the topoisomerase-1 inhibitor P1021 is released, and inhibits DNA topoisomerase-1 activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of TROP-2-expressing tumor cells. TROP-2 is a transmembrane protein overexpressed in various tumors. Its expression is associated with enhanced tumor aggressiveness, metastasis, drug resistance and increased tumor cell survival.