AsianScientist (Sep. 13, 2011) – The leading cause of death by cancer is cancer metastasis – the rapid and often fatal spread of cancer cells from the primary tumor to other parts of the body.
In the latest issue of Science Translational Medicine, scientists at A*STAR’s Institute of Molecular and Cell Biology (IMCB) have made a landmark discovery in the battle against the rapid spread of aggressive cancers.
Contrary to the current accepted theory that antibodies can only bind to cancer proteins found on the cancer cell surface, the IMCB team led by Dr. Zeng Qi is the first to discover that antibodies can in fact directly target intracellular oncoproteins that reside within the cancer cells.
PRL-3, which stands for Phosphatase of Regenerating Liver 3, is a key protein linked to cancer metastasis. PRL-3 is commonly overproduced in many types of aggressive lung, liver, kidney, bone, and breast cancer, making the protein an ideal target for cancer diagnostics and treatment.
Traditionally, oncoproteins like PRL-3 phosphatase which reside within the cancer cells were thought to be inaccessible by antibodies because it is widely accepted that antibodies are too big to cross the cell membrane.
“We are very excited because this study showed for the first time that it is possible to successfully suppress cancer growth by direct targeting of intracellular oncoproteins, such as PRL-3, with the respective cancer-specific antibodies,” said Dr. Zeng, who first identified PRL-3 phosphatase in 1998.
By directly introducing PRL-3 antibodies into the mice, the scientists observed a 70 to 90 percent reduction of tumors caused by PRL-3 expressing cancer cells. This significant reduction is also achieved by vaccinating the mice with PRL-3 antigens to produce PRL-3 specific antibodies.
To prove that antibodies can indeed directly target other intracellular oncoproteins as a general phenomenon, the team also performed the experiment with two different representative intracellular proteins, EGFP and mT oncoprotein.
“This means that a whole new list of intracellular oncoproteins previously thought to be untargetable by therapeutic antibodies or vaccinations can now be potentially targeted. This will expand the scope for tailor-made antibody therapy as well as usher in a new era of tailor-made cancer vaccines,” added Dr. Zeng.
The article can be found at: Guo K et al. (2011) Targeting Intracellular Oncoproteins with Antibody Therapy or Vaccination.
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Source: A*STAR.
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