Sep 132011
 
Normal cancer cell division from NIH

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Cancer: Antibodies Can Directly Target Oncoproteins Inside Cancer Cells to Suppress Aggressive Cancer Growth

Scientists at A*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 associated with PRL-3 oncoprotein[1].

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 like PRL-3 that reside within the cancer cells to suppress cancer growth successfully. This breakthrough finding will pave the way for more targeted solutions for cancer treatment and also offers hope for cancer prevention.

The leading cause of death by cancer is cancer metastasis — the rapid and often fatal spread of cancer cells from the primary tumour to other parts of the body. 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. For example, colorectal cancer and breast cancer, the top five most deadly cancers in the world[2] and also the number one most common cancers in both male and female population respectively in Singapore[3], are frequently associated with elevated levels of PRL-3 phosphatase. PRL-3 is therefore 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. This study suggests that cancers could be effectively treated through the direct introduction of antibodies to target the PRL-3 oncoprotein inside the cancer cell. Likewise, vaccination with PRL-3 antigen to prevent cancer can be administered to induce the body’s immune system to produce PRL-3 antibodies that will directly target the PRL-3 oncoprotein within the cancer cell.

Said Dr Zeng, who first identified PRL-3 phosphatase in 1998, “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.” Using mouse models in this study, by directly introducing PRL-3 antibodies into the mice, the scientists observed a 70% to 90% reduction of tumours caused by PRL-3 expressing cancer cells. This significant reduction is also achieved by vaccinating the mice with PRL-3 antigen[4] to produce antibodies that could specifically target PRL-3-expressing cancer cells.

To demonstrate 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[5] and mT[6]oncoprotein. It was observed that the antibodies introduced to the mice could directly target the intracellular oncoproteins to dramatically retard tumour progression.

Added Dr Zeng, “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.”

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