Definition

An antibody-drug conjugate (ADC) containing a fully human monoclonal antibody, directed against the extracellular domain of the human CD70 molecule, conjugated to a prodrug of a CC-1065 (rachelmycin) analogue via a stable peptide-based linker, with potential antineoplastic activity. The anti-CD70 antibody moiety of the anti-CD70 antibody-drug conjugate MDX-1203 selectively binds to the extracellular domain of CD70 on tumor cell surfaces. Upon internalization, the prodrug moiety is released and activated and binds to double-stranded B-DNA within the minor groove, thereby alkylating the –3 position of adenine, which may result in the inhibition of cellular proliferation of tumor cells that overexpress CD70. CD70, the ligand for the costimulatory receptor CD27 and a member of the tumor necrosis factor (TNF) family, is found on the surfaces of various types of cancer cells. The antitumor antibiotic CC-1065, a DNA minor-groove-binding alkylating agent, was originally isolated from the bacterium Streptomyces zelensis.