Cheng William Hong1 and Qi Zeng2,3
1 - Cleveland Clinic Lerner College of Medicine, 9500 Euclid Avenue, Cleveland, OH 44195, USA
2 - Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research),
61 Biopolis Drive, Proteos, Singapore 138648, Republic of Singapore
3 - Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Republic of Singapore
Published online in Cancer Research on 19 July 2012.
A major challenge in cancer therapy is the lack of specificity for cancer cells. Antibody-based therapies have better specificity and thus improved efficacy over standard chemotherapy regimens. Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and are proven agents for recognizing and destroying malignant cells. However, the development of antibody therapies has focused only on targeting extracellular (cell surface or secreted) proteins rather than intracellular targets (within cells, such as phosphatases/kinases and transcription factors) because antibodies are generally believed to be too large to enter cells, resulting in a large untapped source of intracellular therapeutic targets. Recently, we presented evidence that suggests intracellular proteins with high expression in cancer cells are useful targets for mAb-based or vaccination immunotherapies, thus challenging current understanding. Here, we further discuss the concept and future uses of these immunotherapies against a large pool of intracellular oncoproteins for cancer therapy. This line of research has the potential to vastly expand the field of antibody therapy and usher in a new era of cancer vaccines.
Three possible mechanisms for antibody targeting intracellular antigens in cancer cells.
A. Antibodies may potentially enter PRL-3 expressing cells to target intracellular PRL-3 and neutralize its function.
B. Some of the intracellular PRL-3 may be externalized and displayed on the surface of cancer cells by unconventional secretion.
C. Proteolytic fragments of intracellular PRL-3 may be presented by MHC class I molecules to attract cytotoxic T lymphocyte (CTL).
For more information on Qi ZENG's lab, please click here.