Anti-ADAM9/Exatecan Antibody-drug Conjugate MGC028

**Semantic type:** Pharmacologic Substance

**Definition:** An antibody-drug conjugate (ADC) composed of a humanized monoclonal antibody directed against the tumor-associated antigen (TAA) a disintegrin and metalloproteinase domain 9 (ADAM9), site-specifically conjugated at asparagine 297 of the heavy chain through enzymatic glycan remodeling, via a cleavable bicyclononyne carbamoyl sulfamide Val-Ala-PABC linker, to the cytotoxic DNA topoisomerase I inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-ADAM9 ADC MGC028, the anti-ADAM9 monoclonal antibody moiety targets and binds to ADAM9 on tumor cells. Upon binding, internalization, and linker cleavage, exatecan is released and inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. MGC028 is also able to induce a bystander effect on neighboring cells in the tumor environment. This further inhibits the proliferation of tumor cells. ADAM9, belonging to the ADAM family of proteases, plays a key role in cytokine and growth factor shedding and cell migration. It is overexpressed on multiple solid tumors while minimally expressed on normal tissue. Dysregulation of ADAM9 has been implicated in tumor progression, migration and metastasis. Its expression is correlated with poor prognosis. MGC028 does not bind Fc-gamma receptors.

**Synonyms:** - Anti-ADAM9 ADC MGC028 - MGC 028 - MGC-028 - MGC028