Transmembrane TNF-α preferentially expressed by leukemia stem cells and blasts is a potent target for antibody therapy

Zhou X et al, 2015 Blood                                                             

Link to abstract: http://www.bloodjournal.org/content/126/12/1433

Transmembrane tumor necrosis factor-a (tmTNF-a) in leukemia is preferentially expressed in leukemia cells of human bone marrow samples with AML (n = 69), B- or T-ALL (n = 30) compared to non-malignant anemia (n = 30). TmTNF-a+ expression seemed to correlate with poor prognosis. Knockdown of tmTNF-a+ expression rendered leukemia cells more sensitive to chemotherapy in vitro and delayed regeneration of leukemia in a mouse model. These mice transplanted with leukemia cell lines were treated with a monoclonal antibody targeting tmTNF-a. This resulted in leukemia cell killing via antibody-dependent cell-mediated and complement-dependent cytotoxicity in vitro and inhibited leukemia cell growth in vivo while simultaneously sparing normal hematopoietic cells.

*TmTNF-a represents a novel target antigen in acute leukemia.