anti-GD2 antibody-drug conjugate M3554

An antibody-drug conjugate (ADC) composed of the humanized monoclonal antibody dinutuximab (ch14.18) directed against the tumor-associated antigen (TAA) disialoganglioside (GD2; GD-2) conjugated, via a cleavable beta-glucuronide linker, to the camptothecin analog and topoisomerase 1 inhibitor exatecan, with potential antineoplastic activity. Upon administration of anti-GD2 ADC M3554, dinutuximab targets and binds to GD2 expressed on tumor cells. Upon binding, internalization and linker cleavage, exatecan is released. Exatecan inhibits DNA topoisomerase 1 activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. This inhibits the proliferation of GD2-expressing tumor cells. GD2 is overexpressed in certain tumor types including neuroblastoma, osteosarcoma, glioma and soft tissue sarcoma.