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ESK1-New Monoclonal Antibody Targets Intracellular Oncogenic Proteins in Leukemias

Michael Kaufman | March 26, 2013 'While WT1 is overexpressed in leukemias and other cancers, including myeloma, and breast, ovarian, and colorectal cancers, it is found in few healthy cells, which makes side effects less likely to occur from drugs that target it. “This is a new approach for attacking WT1, an important cancer target, with an antibody therapy,” said lead author David A. Scheinberg, MD, PhD, chair of the Sloan-Kettering Institute's molecular pharmacology and chemistry program and an inventor of the antibody. “This is something that was previously not possible. There has not been a way to make small-molecule drugs that can inhibit WT1 function. Our research shows that you can use a monoclonal antibody to recognize a cancer-associated protein inside a cell, and it will destroy the cell.”

“This is a new approach for attacking WT1, an important cancer target, with an antibody therapy,” said lead author David A. Scheinberg, MD, PhD, chair of the Sloan-Kettering Institute's molecular pharmacology and chemistry program and an inventor of the antibody. “This is something that was previously not possible. There has not been a way to make small-molecule drugs that can inhibit WT1 function. Our research shows that you can use a monoclonal antibody to recognize a cancer-associated protein inside a cell, and it will destroy the cell.”
In the current study, “ESK1 bound to several leukemia and solid tumor cell lines and primary leukemia cells,” wrote the authors. “Low doses of naked ESK1 antibody cleared established, disseminated, human acute lymphocytic leukemia and Philadelphia chromosome–positive leukemia in nonobese diabetic/severe combined immunodeficient γc−/− (NSG) mouse models. At therapeutic doses, no toxicity was seen in HLA-A0201 transgenic mice.”
“We were surprised that the antibody worked so well on its own,” said Scheinberg. “We had originally expected that we might need to use the antibody as a carrier to deliver a drug or a radioactive therapy to kill the cancer cells, but this was not necessary.”...'

Full article here:
http://www.cancernetwork.com/leukemia-lymphoma/content/article/10165/213...