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Print ArticleAn engineered virus tracks down and infects the most common and deadly form of brain cancer and then kills tumor cells by forcing them to devour themselves, researchers at The University of Texas M. D. Anderson Cancer Center report this week in the Journal of the National Cancer Institute.
The modified adenovirus homed in on malignant glioma cells in mice and induced enough self-cannibalization among the cancer cells -- a process called autophagy -- to reduce tumor size and extend survival, says senior author Seiji Kondo, M.D., Ph.D., associate professor in the Department of Neurosurgery at M. D. Anderson.
''This virus uses telomerase, an enzyme found in 80 percent of brain tumors, as a target,'' Kondo says. ''Once the virus enters the cell, it needs telomerase to replicate. Normal brain tissue does not have telomerase, so this virus replicates only in cancer cells.''
Other cancers are telomerase-positive, and the researchers showed in lab experiments that the virus kills human prostate and human cervical cancer cells while sparing normal tissue.
In addition to demonstrating the therapeutic potential of the virus, called hTERT-Ad, Kondo says the international research team also clarified the mechanism by which such conditionally replicating adenoviruses (CRAs) infect and kill cancer cells.
Autophagy is a protective process that cells employ to consume part of themselves when nutrients are scarce or to destroy some of their organelles to recycle their components. A double membrane forms around the material to be consumed, then everything inside is digested.
Kondo and colleagues showed that hTERT-Ad (short for human telomerase reverse transcriptase promoter regulated adenovirus) infected the glioma cells and induced autophagy by inactivating a molecular pathway -- the mammalian target of rapamycin (mTOR) pathway -- that is known to prevent cellular self-cannibalization.
The result was a huge difference in tumor volume among mice with subcutaneous malignant glioma that got hTERT-Ad and those that received a different, non-replicating virus. Average tumor size in the hTERT-Ad group was 39 cubic millimeters, while those receiving the other virus had an average tumor volume of 200 cubic millimeters.
Among mice with malignant gliomas in the brain, those treated with three injections of hTERT-Ad on average lived 53 days. Those receiving the control adenoviruses lived on average 29 days. Two of the hTERT-Ad mice survived 60 days and had no detectable brain tumors.
Analyses of dead cancer cells showed telltale signs of autophagy: bits of virus in the cell nucleus and autophagic vacuoles -- cavities with residual digested material.
The cells showed no sign of having been killed by apoptosis -- a much better known process of programmed cell death. A normal biological defense mechanism that systematically kills defective cells, apoptosis is suppressed or dysfunctional in cancer cells. Many cancer therapies focus on restoring or enhancing apoptosis to combat the disease.
''We believe that autophagy, but not apoptosis, mediates the principal anti-tumor effect of conditionally replicating adenoviruses,'' Kondo says.
Cells killed by apoptosis show specific damage to the cell nucleus and DNA, with other cellular organelles preserved, Kondo explains. Cells killed by autophagy have little damage to the nucleus but heavy degradation of the cells' organelles.
Apoptosis and autophagy should be viewed as type 1 and type 2 versions of programmed cell death, Kondo says. In a Nature Reviews Cancer paper last September, Kondo and colleagues reviewed therapies and molecules that cause or inhibit the self-cannibalization process and compared autophagy and apoptosis, which has been more heavily studied.
To improve cancer therapeutics, Kondo and colleagues concluded that it is vital to identify molecules that regulate autophagy in cancer cells and to understand how autophagy is associated with cell death, a relatively new field in cancer research.
The research group is following up the malignant glioma findings by studying ways to improve the efficiency of viral infection of cancer cells.
Source : University of Texas M. D. Anderson Cancer Center
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Thats really cool and interesting.
Super awesome.
How do you then kill the engineered virus after it's done?
and we'll never see it on the market...unless you have one-gatrillion dollars.
Isn't it possible for this virus to mutate like other viruses....in other words is it possible, considering mutation, for this virus to mutate to the point where it finishes off the tumor cells THEN attacks the normal, healthy cells?
good call. i wonder if you can stop the development of antibodies so the virus just exists in everyone and stops cancers developing in the first place
The virus couldn't live in people like you suggest. It depends on the cancer cells to replicate - no cancer, no replication.
Cancer is a VERY lucrative disease for the medical community. I seriously have doubts that they'll ever let it be cured. That Gatrillion dollars likely needs to come from us taxpayers.
yes and no, the payment of the actual treatment will probably cost more thatn a million until other companies are able to do it, then there will be an easier and safer way to treat it by then, and the research, tax breaks, and actual clinical studies will come from the tax payers.
I hope this treatment can be developed further. This type of cancer killed my father 10 years ago and is still virtually a death sentence today. There may be problems using this therapy on patients of child bearing age since telemorase is active in germ cells (e.g. ova and sperm). Otherwise sounds great for patients over 40 years of age (who also happen to be the group with the lower survival rates for gliomas).
Anonymous (unregistered) writes:
and we'll never see it on the market...unless you have one-gatrillion dollars.
05/03/2006 05:28 pm
Not necessarily so. Most scientists aren't as money hungry as people tend to think. The problem would be getting FDA approval, but something that's potentially that beneficial? If it's feasible and safe, it'll be available just like any other treatment.
There is the possibility of mutation. Viruses have various methods by which they mutate. This includes through the incorporation of viral coats of other non-related viruses. This can lead to the development of new viruses with properties of both viruses. This is especially of concern considering that most cancers are of viral origin. For instance Leukemias can becaused by the HTLV family of viruses. The human papilloma virus can cause cervical cancer. B cell lymphoma is caused from Epstein Barre' virus. Hepatitis viruses can cause liver cancer. One form of Kaposi's sarcoma is viral in origin, the other form has a bacterial origin. Simian virus type 40, that contaminated the polio vaccines given to over 90 million Americans, causes brain cancer, liver cancer, bone cancer, etc. An article in Scientific American a while back even stated the fact that every oncogene (genes that cause cancer) found to date was viral, and that no human oncogene had ever been found. Another fact along the same lines is that the first cancer virus was found in 1910 by Peyton Rous, thoughhe did not receive the Nobel Prize for his discovery for over 65 years because the medical establishment did not want to admit to the viral link of cancer, nor the fact that cancer can be contagious. Luckily, viruses like these cannot infect healthy immune systems.
And if for some reason that it did work with a high success rate we would never see it on the market. Unfortunately we have an extremely corrupt medical system, which includes illegal investments of FDA officials in to the drug companies they overlook, a violation of insider trading laws.
If an effective cancer cure were ever put on the market medical schools would go under due to the loss of grants, researchers would stop receiving grants that they use to live on, and groups like the American Cancer Society would lose over $4 billion a year, in donations, that goes almost exclusively to executive salaries and travel. This helps to explain the ACS has never come up with even a single advancement in cancer research.
In fact numerous effective cancer cures have been brought forth over the years, yet they never seem to get to market. This is especially true for ozone therapy, which was started in Germany in 1892, and came to the US in 1898. Since this therapy preceeds the formation of the FDA, and happens to be one of the safest therapies on the market, under the law it has a grandfathered approval status. Yet the FDA routinely violates the law by jailing those who perform ozone therapy. Chemically ozone destroys cancer through multiple mechanisms. First of all malignant tumors lack the protective antioxidant enzymes catalase, glutathione peroxidase, selenium methionine peroxidase, and superoxide dismutase, which protect healthy cells. When ozone reacts with the lipid membrane of the cells a lipid peroxide is formed. Hydrogen peroxide is also formed by the reaction of ozone with water. These peroxides enter in to all cells. The antioxidant enzymes in the healthy cells break down the peroxides in to water and oxygen. Cancer cells on the other hand cannot break down these peroxides, thus these cells swell up and burst. Secondly the peroxides stimulate white blood cell activity. In fact NK (natural killer) cells use peroxide in the same manner to kill cancer cells. Ozone, being a strong oxidizer, kills cancer microbes, and carcinogens, such as xenoestrogens. As far as safety goes, a study done in Germany followed over 6.5 million doses of ozone given for therapy. There were slightly over 30adverse reactions reported, mostly due to improper administration. Therefore, no therapy can match effectiveness and safety of ozone for cancer treatment. Which is also why the medical establishment has fought so hard to keep it from the market.
This is a concern I has as well. I am a student and very interested in biotech, genenetics and viruses.
Engineered viruses should only contain partial nucleic acid sequences. An engineered virus, this is only my gatherings, should only contain the genes needed for cell identification and the info as for what to do within the targeted cell. I would hope that these viruses wouldn't have sufficient info for any replication outside of the targeted cells.
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