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Use of Anti-Prion Antibody in Ovarian Cancer
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Prion (a combined, shortened, and mis-spelled form of protein of infection) is a name given to a misfolded protein that is generally associated with neurological disease. Prions have been associated with a set of diseases called Transmissible Spongiform Encephalopathies (TSEs), including Mad Cow disease, variant Creutzfeldt-Jakob disease, and Kuru. All of these diseases result from incorrectly folded proteins that appear to be able to induce nearby proteins to misfold as well. The resulting accumulation of improperly folded proteins results in large clumps of proteins, called amyloid fibers, which form plaques in the brain, resulting in disease. TSEs are characterized by a sponge-like appearance of the brain tissue. There is currently no treatment available, and all TSEs are fatal.

Prions were originally described by Stanley Prusiner, and the concept of proteins causing infection was initially met with skepticism. However, years of research have demonstrated that proteins may indeed be able to cause neighboring proteins to misfold, resulting in disease. What is unique about TSEs is that the infectious agent, the prion, is made only from protein. Unlike other infectious agents, such as bacteria, viruses, and fungi, prions have nucleic acid genome. Even without DNA or RNA genomes to pass on information, prions are transmissible from one individual to another.

In recent years, however, researchers have noted improperly folded proteins being expressed on tumor cells. A tumor suppressor protein known as p53 is commonly mutated in many different types of cancer. Scientists have shown that a specific mutated form of p53 seems to form prion-like amyloid aggregates on breast cancer cells, in addition to other cancer cell types. It is yet not clear if the mutated p53 is able to induce misfolding of normal p53 molecules on nearby cells, thereby helping spread the cancer, or if the aggregates are the result of changes to the DNA sequence of p53. Regardless, amyloid forming misfolded p53 proteins are an exciting new ground in cancer research. Researchers plan on investigating this correlation between misfolded p53 and the development of cancerous cells, and potentially utilize this mutated prion-like p53 protein as a therapeutic target. Scientists also want to determine if preventing p53 protein aggregates from forming on cells can prevent the development of cancerous cells.

Recently, a company called Amorfix Life Sciences Ltd, of Toronto, Canada, and specializing in early-stage product development of therapeutics, announced new data suggesting that standard chemotherapeutic agents used during cancer treatment may actually increase the amount of misfolded p53 aggregates on ovarian cancer cells, but not normal ovarian cells. In addition, preliminary results have indicated that treatment with an anti-misfolded p53 antibody can reduce tumor volume. By combining standard chemotherapeutic agents, to increase expression of misfolded p53 on cancer cells, and the anti-misfolded p53 antibody to target the cancer cells, researchers at Amorfix hope to have increased therapeutic efficacy against ovarian cancer tumors, compared to using either therapy individually. Studies involving co-treatment with chemotherapy and antibody are beginning in order to determine the efficacy of the combined therapy, compared to either therapy administered alone against ovarian cancer.

The advent of novel therapeutic strategies is particularly exciting for ovarian cancer. Treatment of solid tumors, such as those that cause ovarian cancer, are difficult due to the complexity of the tumor environment. In addition, ovarian cancer is often called a “silent killer.” Early stage symptoms of ovarian cancer are very subtle, and are not easily recognized by the patient as something serious. Ovarian cancer is thus not normally detected until it has reached an advanced stage, which makes treatment especially difficult. Chemotherapies are not as effective against late stage ovarian cancer. Combinations therapies, such as the one discussed above, are very attractive as they may provide better therapeutic benefits to the patient.

Targeted immunotherapeutics such as the combination therapy mentioned above are very promising in cancer research. Conventional cancer therapies involve chemotherapeutic agents that kill all rapidly dividing cells, including healthy cells as well as cancer cells. This undirected killing results in undesirable side effects, including severe nausea, weight loss, and anemia, and compromises the host’s immune system. By utilizing specific targets on cancer cells, such as the misfolded p53 aggregates, antibody immunotherapies can directly target and kill cancer cells, leaving normal cells unharmed and preventing side effects that occur with conventional cancer therapeutics.

References:
http://finance.yahoo.com/news/amorfix-an...00373.html
http://medicalxpress.com/news/2012-06-pr...lding.html
http://biotech.about.com/b/2010/09/24/th...cancer.htm
http://www.cdc.gov/ncidod/dvrd/prions/
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Use of Anti-Prion Antibody in Ovarian Cancer00