Antibody-based therapeutics targeting cd33, cd45, and cd66

Abstract

Targeted therapy of acute myeloid leukemia (AML) with monoclonal antibodies (MoAbs) has thus far been mostly directed at CD33, CD45, and CD66. The notion that some AMLs may predominantly or entirely involve committed CD33+ myeloid precursors provided the rationale for eradicating underlying stem cells with anti-CD33 antibodies. Emerging data demonstrating efficacy of the anti- CD33 immunoconjugate, gemtuzumab ozogamicin, in acute promyelocytic leukemia and other favorable- and intermediate-risk AMLs validate CD33 as drug target. Unlike CD33, CD45 and CD66 are noninternalizing antigens and have primarily been targeted to deliver radionuclides to sites of hematopoietic tissue, particularly to augment pre-transplant conditioning regimens. Early studies document the feasibility of this approach in selected patients, although future controlled studies will need to assess whether this strategy indeed leads to improved outcomes. Given this encouraging clinical experience, the use of MoAbs is likely expanding significantly in the future with identification of additional AML (stem) cell-associated antigens.