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Mar 28, 2013
 |  BC Innovations  |  Targets & Mechanisms

mAb attack on WT1

Wilms tumor 1 is overexpressed in many different cancers, but most antibody and small molecule developers have deemed it undruggable because it is an intracellular transcription factor. Now, researchers at Eureka Therapeutics Inc. and the Memorial Sloan-Kettering Cancer Center have targeted Wilms tumor 1-positive cancer cells with a mAb against peptide fragments derived from the protein that are presented on the cells' surface.1

The biotech hopes to have the mAb in a Phase I trial in leukemia within two years and is seeking a clinical development partner.

Wilms tumor 1 (WT1) is a transcription factor found in the cell nucleus that is overexpressed in a range of leukemias and solid tumors. Ongoing efforts to address WT1-positive cancers have focused on vaccines and T cell therapies as opposed to antibodies and small molecules.

Antibodies are unable to target intracellular proteins, whereas small molecules typically cannot modulate the protein-protein interactions in which transcription factors are involved.

In 2006, research teams led by David Scheinberg, chair of the Molecular Pharmacology & Chemistry Program at the Sloan-Kettering Institute at MSKCC, published a pair of studies identifying a series of nine-amino-acid, WT1-derived peptides that could be used to trigger a T cell immune response against some WT1-positive cancer cells.2,3 The peptides are processed and presented on the cell surface in a complex with a specific human leukocyte antigen (HLA) molecule called

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