Anti-Human CD22 (Inotuzumab) – Fc Muted™ (C1015-500ug)

CD22 is a sialic-acid-binding immunoglobulin-like lectin (Siglec) that acts as an endocytic receptor1. CD22 mediates intercellular interactions for sialic acid-bearing ligands and modulates B cell activation and antigen receptor signaling2. CD22 is considered an attractive target for conjugated antibody chemotherapeutic development because it is rapidly internalized when bound. 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 agent2. The semisynthetic derivative N-acetyl-γ-calicheamicin dimethyl hydrazide (Calich-DMH; calicheamicin) is used as an enediyne antitumor antibiotic in CD22-based chemotherapy3. Inotuzumab is composed of humanized CD22-directed monoclonal antibody G5/44 covalently attached to Calich-DMH via an acid-cleavable linker2, 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 groups2. When Inotuzumab binds CD22-expressing tumor cells, the inotuzumab-CD22 complex is rapidly internalized and the acidic intracellular environment triggers the release of Calich-DMH6, 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 apoptosis2. 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 cells4, 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 IgG45. Inotuzumab has been approved for the treatment of some patients with CD22-positive B-cell precursor acute lymphoblastic leukaemia6. This research-grade biosimilar is not covalently bound to Calich-DMH.