CMC-544 (inotuzumab ozogamicin): A CD22-targeted immunoconjugate of calicheamicin

CMC-544 (Inotuzumab ozogamicin) is a CD22-targeted immunoconjugate of calicheamicin currently being evaluated in phase III clinical trials in patients with non- Hodgkin’s B-cell lymphoma. CMC-544 is the product of a collaboration between Wyeth and UCB-Celltech. CMC-544 has demonstrated significant clinical activity in both follicular and diffuse large B-cell lymphoma patients who had failed multiple therapies.1,2 CMC-544 (Figure 1) is a humanized IgG4 anti-CD22 antibody (G5/44) covalently linked to N-acetyl gamma calicheamicin dimethyl hydrazide (CalichDMH) via an acid-labile 4-(4-acetylphenoxy)butanoic acid (AcBut) linker.3,4 CD22 is a Blymphoid lineage-specific differentiation antigen expressed on the surface of both normal and malignant B cells. CD22 is not expressed on hematopoietic progenitors of the B-lymphoid lineage. CD22 efficiently internalizes upon binding to an antibody making it an ideal candidate for targeted drug delivery. Targeting malignant B-cells through CD22 by the CD22 specific antibody G5/44 could, therefore, be an efficient way to deliver calicheamicin to destroy malignant B-cells.