Abstract
Reaching Un-Drugable Intracellular Targets with the Long Arm of Antibodies
Highlights
The vast majority of cellular proteins, many of which are the most interesting and important molecules for regulating normal and neoplastic growth, lie within the cell, hidden from monoclonal antibody therapeutics by the barriers of the plasma membrane
We recently demonstrated in vivo the successful treatment of several human cancers by use of a human “T cell receptor (TCR)-like” monoclonal antibody (mAb) to the intracellular oncogenic protein, WT1, a difficult to drug cancer target
Intracellular proteins are usually degraded by the proteasome or endo/lysosomes, and the resulting specific peptide fragments bind to MHC class molecules
Summary
The vast majority of cellular proteins, many of which are the most interesting and important molecules for regulating normal and neoplastic growth, lie within the cell, hidden from monoclonal antibody (mAb) therapeutics by the barriers of the plasma membrane. We recently demonstrated in vivo the successful treatment of several human cancers by use of a human “TCR-like” mAb to the intracellular oncogenic protein, WT1, a difficult to drug cancer target The exquisite specificity of mAb is prevented from addressing some of the only truly specific cancer targets, such as mutated signaling molecules and transcription factors, fusion-protein oncogenes and many other tumor associated antigens.
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