CHICAGO – A therapeutic target and possibly a treatment for acute myeloid leukemia and myelodysplastic syndrome may lie in the immortalized B cells of a patient whose acute myeloid leukemia was cured after allogeneic stem cell transplantation.
A B cell clone isolated from this patient makes a hypermutated immunoglobulin G1 antibody that binds leukemic blasts of all World Health Organization 2008 AML and myelodysplastic syndrome (MDS) types, based on cells obtained from 60 AML or MDS patients, but does not target healthy cells and lymphoid tissue, Mette D. Hazenberg, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.
The antibody, called AT1413, targets sialylated CD43, an antigen that is overexpressed in AML and MDS blasts. Unlike commercial CD43 antibodies, which target Jurkat lymphocytes and THP-1 cells, AT1413 only targets THP-1 cells. While AT1413 binds to endothelial cells and granulocytes, it does not kill these cells. It does, however, kill SH2 AML cells.“CD43 is broadly expressed on AML and MDS and, therefore, is a highly interesting target for immunotherapy,” said Dr. Hazenberg of AIMM Therapeutics and Academic Medical Center, Amsterdam.
The growth of luciferase-labeled AML cells expressing CD43s was inhibited in highly immunodeficient NOD scid-gamma mice that were reconstituted with human hematopoietic stem cells injected with AT1413. Healthy human hematopoietic cells, which express low levels of the target, were not affected by the treatment.
Next steps include further in vivo preclinical studies, according to Dr. Hazenberg.
AIMM Therapeutics is a biotech company comprising a joint venture between Immpact and the Academic Medical Center (AMC) at the University of Amsterdam. The study was supported by an AMC PhD scholarship and the KWF Dutch Cancer Society.
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