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Oncolytic Virotherapy -- The Most Promising Cure for Cancer?

This information is directly paraphrased from Cell Genesys Inc., a company focused on the development and commercialization of novel biological therapies for patients with cancer.  If I had to put my money on a future cancer cure with the best chance for success, this is the technology I'd pick.

Oncolytic ("onco" meaning cancer, "lytic" meaning "killing") viruses represent an innovative cancer therapy known as "virotherapy"—a therapy that seeks to harness the natural properties of viruses to aid in the fight against cancer.

The notion of using a virus in the fight against cancer has existed for many decades. In the 1940s and 50s, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumors. In 1956, one of the first human clinical trials with an oncolytic virus was conducted in patients with advanced stage cervical cancer. Although the results were promising, research in this arena was delayed due to the lack of technologies needed to purify viruses and to safely deliver the viral treatment. It was not until 1991, following a publication in Science magazine about a study conducted at Georgetown University that used the herpes simplex 5 virus for the treatment of brain cancer, that new attention was focused on virotherapy.

In short, oncolytic viruses are human viruses that infect and replicate in cancer cells, destroying these harmful cells and leaving normal cells largely unaffected. Like all viruses, oncolytic viruses seek to penetrate a host cell and "trick" it into replicating more of the virus until ultimately, it bursts. However, unlike other viruses, oncolytic viruses seek only to replicate in cancer cells.

Research is currently being conducted by institutions around the world using both "non-engineered" and "engineered" viruses to evaluate their use in the fight against multiple types of cancer. Non-engineered viruses are naturally occurring viruses that innately and preferentially target certain types of tumor cells. Some non-engineered viruses include the Newcastle Disease Virus, Autonomous Parvovirus, and the Reovirus. Conversely, some other viruses which do not normally target cancer cells are "re-engineered" to do so. Scientists genetically modify the virus to replicate within specific types of cancer cells. Today, three main approaches are being explored in the development of engineered tumor-specific oncolytic viruses:

●     Selective Targeting—Capsid Protein Modification: The capsid protein, the external surface of the virus, is modified so that the virus will specifically target cancer cells, completely avoiding normal cells. The virus would then replicate within the targeted cancer cell, ultimately leading to cell death.

●     Selective Replication in the Absence of an Antitumor Gene: The virus is genetically modified so that it will replicate only in the absence of a gene believed to inhibit tumor cell growth, such as P53. While the virus "passes through" normal cells, it is triggered to replicate in cancer cells that do not exhibit an antitumor gene, ultimately leading to cancer cell death.

●     Selective Replication in the Presence of Unique Tumor Cell Characteristic: The virus is genetically modified so that it will replicate only in the presence of a characteristic (e.g. an antigen) unique to the specific type of cancer. While the virus passes through normal cells, it is triggered to replicate in cancer cells that exhibit a specific characteristic, ultimately leading to cancer cell death.

Examples of viruses that are re-engineered to work in this fashion include the adenovirus, the herpes simplex virus-1, influenza, and the vaccinia virus.

Oncolytic viruses use multiple mechanisms of action to kill cancer cells. Once the virus infects the tumor cell, it compromises the cell's natural defense mechanisms, giving the virus extra time to thrive. The virus then begins to replicate. The virus continues to replicate until finally the tumor cell can no longer contain it and "lyses" (bursts). The tumor cell is destroyed and the newly created viruses are spread to neighboring cancer cells to continue the cycle. It is important to remember that all oncolytic viruses are intended to replicate only in cancer cells and to pass through normal tissue without causing harm. Once all the tumor cells are eradicated, the oncolytic virus no longer has a viable site in which to replicate, and the immune system eventually clears it from the body.

Clinical data suggest that oncolytic viruses will offer significant therapeutic advantages over existing cancer therapies such as chemotherapy and radiation. The primary benefits identified to date include the following:

●     High Therapeutic Index: Compared with traditional therapies, oncolytic viruses have been shown to have a high therapeutic index. In some instances, the therapeutic index of such viruses has been found to be as high as 100,000 to one. In other words, for every 100,000 tumor cells that are killed, only one normal cell is killed. This is significantly higher than the therapeutic index commonly seen with chemotherapy—six to one—and may result in greater efficacy with fewer side effects.

●     Better Antitumor Efficacy due to Viral Replication: Unlike some traditional therapies that are cleared from the body within a specific amount of time (e.g. chemotherapy), oncolytic viruses are engineered to proliferate and remain in the body until all of the cancer cells are destroyed. This self-proliferation reduces the need for extensive re-treatment and results in greater efficacy and patient convenience.

●     Synergistic Antitumor Activity with Other Cancer Therapies: Some oncolytic viruses have been shown to work even better when used in combination with conventional cancer treatments such as radiation and chemotherapy.

This sounds like fascinating stuff to me.  There is something appealing about the notion of sending in small insurgencies of nano-troops to attack cancer cells from the rear, at their own level of operation.  I always thought of cancer cells as actually being "improved" versions of normal cells, overcoming the natural order of individual cell old age & death, multiplying efficiently and taking over territory quickly and effectively.  That is, until the host dies -- at which time cancer doesn't seem so smart, after all.   In this respect, a cancer cell is like a newly evolved viral or bacterial strain, one that hasn't yet learned to improve its long-term reach and effectiveness by not being so virulent to its host. What other replicating life-form is so blasted efficient at multiplying and spreading?  Of course:  viruses!  It sounds like a cool idea to pit them against each other.

   Back to Loose Ends...  

See also my page on bacteriophages.

You can argue whether or not viruses are truly life-forms.  Viruses certainly straddle the gap between life and non-life. They do replicate and contain the genetic material required to do so.  They have simple physical accoutrements to latch onto a cell wall and inject their genetic material into a cell.  That's about all they do.  Their structure is extraordinarily non-complex, almost mechanical in its appearance and operation.  It begs the question as to what life really is.  But because I personally never replicated, I suppose you could make a case that a virus has a stronger basis for being considered alive than I do!


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