Anti-Human CD22 (Inotuzumab) [Clone G5/44],Leinco,C1010

N-acetyl-γ-calicheamicin is a potent, natural cytotoxic agent produced by Micromonospora echinospora that induces double-strand DNA breaks and apoptosis in rapidly proliferating cells, independent of cell cycle progression, and is therefore also of interest as a chemotherapeutic agent 2 . The semisynthetic derivative N-acetyl-γ-calicheamicin dimethyl hydrazide (Calich-DMH; calicheamicin) is used as an enediyne antitumor antibiotic in CD22-based chemotherapy 3 . Inotuzumab is composed of humanized CD22-directed monoclonal antibody G5/44 covalently attached to Calich-DMH via an acid-cleavable linker 2, 4, 5, 6 . The acetyl butyrate linker attaches via an amide bond to surface-exposed lysines of G5/44 and is further stabilized by two methyl groups 2 . When Inotuzumab binds CD22-expressing tumor cells, the inotuzumab-CD22 complex is rapidly internalized and the acidic intracellular environment triggers the release of Calich-DMH 6, 7 . Calich-DMH then binds to the minor groove of DNA, undergoes a structural change in its enediyne moiety that generates diradicals, and induces double-strand DNA breakage, cell cycle arrest and apoptosis 2 . Humanized G5/44 was derived from murine m5/44 by grafting the complementarity-determining regions plus key framework residues onto human acceptor frameworks and then expressing in Chinese hamster ovary cells 4, 5 . The CD22-specific targeting antibody G5/44 carries a S229P mutation in its hinge region that allows it to form stable interchain disulfide bonds and removes the potential for Fab exchange with natural IgG4 5 . Inotuzumab has been approved for the treatment of some patients with CD22-positive B-cell precursor acute lymphoblastic leukaemia 6 . This research-grade biosimilar is not covalently bound to Calich-DMH.