anti-ALPP/ALPPL2/MMAE ADC SGN-ALPV

An antibody-drug conjugate (ADC) composed of h12F3, a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the two oncofetal phosphatases alkaline phosphatase, placental type (ALPP; placental alkaline phosphatase; PLAP), and alkaline phosphatase, placental like 2 (ALPPL2; alkaline phosphatase, germ cell) conjugated, via a protease-cleavable peptide linker, to the microtubule-disrupting cytotoxic agent monomethyl auristatin E (MMAE), with potential antineoplastic activity. Upon administration, the antibody moiety of anti-ALPP/ALPPL2/MMAE ADC SGN-ALPV targets and binds to either ALPP or ALPPL2 or ALPP/ALPPL2 dimer on the surface of tumor cells. Upon internalization and the release of MMAE, MMAE targets and binds to tubulin, and inhibits microtubule polymerization. This results in G2/M phase cell cycle arrest and apoptosis in ALPP and/or ALPPL2-expressing tumor cells. In addition, SGN-ALPV mediates antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). ALPP and ALPPL2, mainly expressed in placenta and testis, form homo- and heterodimers and play key roles in nucleotide recycling. They are overexpressed on certain tumor cell types while normal tissue expression of ALPP and ALPPL2 is restricted to placenta and reproductive tissue.