Description
Calicheamicin is an antitumor antibiotic and is a DNA synthesis inhibitor. It also is a cytotoxic agent that causes double-strand DNA breaks.In vitro activity:PF-06647263 (anti-EFNA4-ADC) is generated via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-γ1 linker-payload with an average drug-to-antibody ratio (DAR) of 4.6. PF-06647263 elicits antigen- and concentration-dependent cytotoxicity, as exposure to PF-06647263 for 96 hours results in cell death (EC50: ~1 ng/mL). In vivo activity:PF-06647263 (0.27, 0.36 mg/kg) results in significant tumor regressions in TNBC xenografts. An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-damaging agent calicheamicin achieves sustained tumor regressions in both TNBC and ovarian cancer PDX in vivo