ANTIBODY-TARGETED CHEMOTHERAPY WITH CMC-544: A CD22-TARGETED IMMUNOCONJUGATE OF CALICHEAMICIN FOR THE TREATMENT OF B LYMPHOID MALIGNANCIES

(Mylotarg ® or CMA-676, a CD33-targeted immunoconjugate of N-acetyl gamma calicheamicin dimethyl hydrazide (CalichDMH, a potent DNA-binding cytotoxic anti-tumor antibiotic) is a clinically validated therapeutic option for AML patients. Here, we describe the preclinical profile of another immunoconjugate of CalichDMH, CMC-544, targeted to CD22 expressed by B lymphoid malignancies. CMC-544 is comprised of a humanized IgG4 anti-CD22 mAb, G5/44, covalently linked to CalichDMH via an acid-labile AcBut linker. Both CMC-544 and unconjugated G5/44 bound human CD22 with subnanomolar affinity. CMC-544, but not unconjugated G5/44, exerted potent cytotoxicity against CD22+ B-cell lymphoma (BCL) cell lines (IC50: 6 to 600 pM CalichDMH). CMC-544 caused a potent inhibition of growth of small but established BCL xenografts leading to cures (therapeutic index>10). CMC-544 prevented the establishment of BCL xenografts and also caused regression of large BCLs (>1.5 g of tumor mass). I