Efficacy &safety of CMA676 in acute myeloid leukemia in final relapse

$0M01FY2000RRNIH

Tufts Medical Center, Boston MA

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Abstract

CMA-676, a conjugate composed of an engineered human anti-DC33 antibody linked to a potent anti-tumor antibiotic, calicheamicin, provides a new method of drug delivery by utilizing a monoclonal antibody to target leukemic cells. The CD33 antigen is a 67 KD glycoprotein that functions as a sialic acid-dependent adhesion protein. CD33 is expressed on normal and leukemic myeloid colony-forming cells (CFC) and on most AML cells, including leukemic clonogenic precursors; however, it is not expressed on normal pre-CFC or pluripotent hematopoietic stem cells. The CD33 antigen is absent from non-hematopoietic tissue. Upon binding of the anti-CD33 antibody, the CD33 antigen is internalized. These properties make it possible to use antibodies against CD33 to specifically deliver agents to leukemic cells. Monoclonal antibody (MoAb) therapy is ideally suited to treatment of leukemia due to the ready accessibility of neoplastic cells in the blood, bone marrow, spleen, and lymph nodes.

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