anti-TROP-2 antibody-drug conjugate PF-06664178

An antibody-drug conjugate (ADC) composed of PF-06478924 (RN926), 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), site-specifically conjugated via a valine-citrulline cleavable linker with the auristatin-based cytotoxic agent Aur0101 (PF-06380101), with potential antineoplastic activity. Upon administration of anti-TROP-2 ADC PF-06664178, the anti-TROP-2 monoclonal antibody moiety PF-06478924 targets and binds to TROP-2 expressed on tumor cells. Upon binding, internalization and linker cleavage, Aur0101 binds to tubulin and inhibits its polymerization, resulting in G2/M phase arrest and apoptosis 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.