anti-MUC1/EGFR bispecific antibody-drug conjugate M1231

An antibody drug conjugate (ADC) composed of a bispecific antibody directed against the tumor associated antigens (TAAs) mucin-1 (MUC1) and human epidermal growth factor receptor (EGFR), conjugated, via a cleavable valine-citruline-based linker, to the hemiasterlin-related toxic warhead, with potential antineoplastic activity. Upon intravenous administration, the antibody moiety of anti-MUC1/EGFR bispecific ADC M1231 targets and binds to MUC1 and EGFR expressed on certain tumor cells. Upon binding, internalization, and enzymatic cleavage, the cytotoxic hemiasterlin moiety of M1231 binds to the vinca domain on tubulin, resulting in inhibition of tubulin polymerization and microtubule assembly, depolymerization of existing microtubules, inhibition of mitosis, and inhibition of cellular proliferation. MUC1 and EGFR, overexpressed on the surface of a variety of cancer cells, play key roles in tumor cell survival and proliferation. MUC1 and EGFR are often co-localized due to loss of membrane polarization on tumor cells while co-expression in normal cells is limited.