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Project Title: Conquering Cancer: The Power of Virotherapy
Project Type: Report Project
One form of biotechnological engineering that has gained a lot of support in recent years is oncolytic virotherapy treatment. Many scientists today believe that oncolytic viruses may contain the answer to ending cancer (Vile et al. 2002, 1). Although this technique has been acknowledged and researched since the 1950’s, the lack of adequate resources and technology did not allow it to progress further (Tong et al. 2012, 5)(Vile et al. 2002, 2). However, the rapid growth of today’s society and its ingenuity has resulted in the reemergence and success of oncolytic virotherapy (Vile et al. 2002, 3). Oncolytic virotherapy is the
process by which certain viruses are introduced into the body. Viruses present an ideal way to attack cancer from the inside. These
viruses selectively infect and break down cancer cells while leaving
normal cells unharmed (Thompson 2013, 1) (Paddock 2013, 1). This targeted treatment makes it
easier to kill tumor cells and lessens the impact of cancer on the body
by eliminating cancerous cells (Paddock 2013, 2). Scientists believe
that engineering oncolytic viruses to act as a biological weapon against
cancer might be able to suppress or eliminate the disease completely. Although there are still many obstacles to get through, this new cancer treatment is starting to
become more widely recognized as its unlimited potential continues to
be tapped in to and developed further (Timmer 2013, 3). The promising results indicate that a solution for cancer may soon be found.
oncolytic virotherapy, scientists alter the genetic makeup of viruses
in order to optimize their chances of destroying, eliminating, and
combating cancer (Thompson 2013, 1), (Timmer 2013, 1).
These viruses are specifically made for this purpose and serve no other
function. The process of oncolytic virotherapy is very complex. Viruses
are engineered in many different ways and forms, each with their own
use (Tong et al. 2012, 1). The most commonly used virus in this method of treatment is the adenovirus (Fikes 2013, 2).
This virus is responsible for causing the common cold and has been
intensively explored. It is particularly appealing because biologists
understand its biological impact after years of treating colds and have
abundantly used the virus in molecular biology and other research
(Nettelback & Curiel 2008, 1).
Adenoviruses also carry favorable, distinct traits. For example, the
genes that they carry into a cell work for a short period of time and
then break down, making them viable candidates for genetic selectivity that does not permanently damage the body.
Viruses can be applied through various means. Methods of applications
include intramural (within a body or organ) delivery, viral vectors, and intravenous injections
(Ferguson 2012, 1). Two main strategies are used during virotherapy in
order to reproduce viruses and kill cancerous cells and tumors. The
first strategy, called transductional targeting, involves scientists
attempting to engineer viruses to selectively infect and eliminate cancerous cells from the body (Nettelback & Curiel 2008, 2). This method is the most commonly used.
The second approach occurs when a small part of DNA, known as a tumor
specific promoter, is placed on the genes of the virus. The promoter
activates and allows the gene to function only in cancer
cells. The virus can enter normal cells, but the promoter will not activate within them, disallowing them to reproduce or kill healthy cells. However, once in the cancer cells, the promoter activates and lets
the virus replicate itself millions of times, rupturing the cancer cells
and spreading to other cancerous cells as the process begins to repeat (Nettelback & Curiel 2008, 3).
Oncolytic virotherapy is very advantageous in many different ways. Some of the benefits of this method are that it is safe, can affect many types of cancer, and advances the medical field further than ever before (Taber & Cheung 2010, 2). Another reason that this method is favorable is because it is more efficient than traditional cancer treatments, such as radiation and chemotherapy (Taber & Cheung 2010, 3). Oncolytic virotherapy kills a lower amount of healthy cells within the body, making it less damaging to important parts of the body such as bone marrow. It can also affect a very broad spectrum of cancer types, making it a diverse and viable option. This method is very efficient at finding and eliminating cancer cells in the body without risking extra damage to other healthy cells that are not a threat (Taber & Cheung 2010, 1). The range at which oncolytic virotherapy is effective is wide. One administration of a dose into an individual’s body can kill a large number of cancer cells and also provide access to tumors within the body that are in hard to reach places (Fikes 2013, 1). Lastly, the symptoms of oncolytic viruses are relatively tame in comparison to how much they help an individual. Within most clinical trials, patients given high dosage levels of oncolytic viruses only suffered flu-like symptoms lasting anywhere from twenty four to forty eight hours (Paddock 2013, 3) (Tong et al. 2012, 4).
Although its potential is evident, using virotherapy to treat cancer also presents some disadvantages. When patients are given multiple doses of virus therapy, the immune system begins to send out antibodies and white blood cells that start to recognize the virus (Ferguson 2012, 4). As a result, subsequent doses end up being less effective because the immune system will immediately lock on to and disable the virus (Vile et. al 2002, 5). One of the major concerns with this form of treatment is that its long term effects are still relatively unknown. In 1999, an 18 year old died after receiving an injection of virotherapy (Nettelback & Curiel 2008, 4). His body shut down after an overwhelming immune reaction to the large dose of viruses he had been given (Nettelback & Curiel 2008, 5). Since virotherapy is relatively new and expanding, scientists are still working on making viruses safer and are taking several precautions (Nettelback & Curiel 2008, 7). However, it is still too soon to determine if there are any significant factors that could permanently damage a patient using this form of therapy. Also, creating these new viruses and altering their genes presents the danger of creating serious mutations or dangerous new diseases altogether (Taber & Cheung 2010, 4). However, these risks are always present in any type of anti-cancer therapy. In order to cure a dangerous and deadly disease, researchers must be able to take risks within reasonable boundaries.
There have been many successful clinical trials of oncolytic viruses as cancer treatment. Many companies involved in oncolytic virotherapy have made significant progress and great strides in the field (Anonymous 2010, 4)(Vile et al. 2002, 4). In clinical trials, different phases are tested. Phase 1 tests are designed to make sure that the drugs are safe for patients receiving them. Phase 2 and 3 trials are performed in order to determine the correct dosage levels and how much power it takes to produce an effect (Nettelback & Curiel 2008, 6). After these phases, the treatment gets reviewed and, if it is approved, eventually gets put on the market.
Onyx-015, developed by Onyx Therapeutics, is one example of a unique virus that is being tested to determine if it has the potential to treat cancer effectively. Onyx-015 was
created by genetically modifying an adenovirus and was extensively
tested in trials to see if it could treat cancer (Thompson 2013, 2). This virus has the
ability to detect the absence of p53, a specific protein with the body
that all cancer cells do not carry (Timmer 2013, 2). As a result of this adaptation, the virus
ignores normal cells and can only attack cancerous cells that lack the p53 protein. Onxy-015 is
currently capable of targeting and destroying half of all major cancer
types but is less effective against others (Vile et al. 2002, 6). This virus has been tested in clinical trials extensively, with
data suggesting that it is safe and selective for cancer (Tong et al. 2012, 2). However, the
drug is ineffective alone and needs to be paired with chemotherapy for
optimal use, somewhat limiting its long term effectiveness (Ferguson 2012, 2). Research
and funding has mostly ceased until the virus can show further potency.
However, one of the most effective clinical trials to date utilizes a genetically engineered vaccinia virus, known as JX-594, as its test subject (Ferguson 2012, 3). This virus is already widely used in vaccinations and has a reputation of being safe, making it a viable candidate to test against cancer. This particular virus was modified in order to make it more cancer selective and also has the ability to increase immune system stimulation Tong et al. 2012, 3). The JX-594 virus works in two different ways. First, the virus recognizes and targets cancerous cells and reproduces inside of them, resulting in their death. Secondly, it helps induce immune responses towards cancerous cells and makes the body attack cancer cells (Fikes 2013, 3). The results, reviewed by analysts, determined that all dosage levels resulted in anti-tumor activity (Tong et al. 2012, 4). Further research showed that a large number of patients displayed some form of resistance to cancer. The average life span of cancer patients utilizing this drug was also increased (Thompson 2013, 3). The JX-594 virus is currently in phase 3 clinical testing and its data looks very encouraging .
Although oncolytic virotherapy has not yet been proven to completely cure the deadly disease of cancer, the success that it has experienced and impact it has made on the medical field has been undeniable. This form of virotherapy shows a promising future as more and more companies and biologists alike continue to invest their time into finding a cure for cancer. Although great strides have been made in this area, there is still plenty of room for more development. More viruses are continuing to be genetically modified and virotherapeutic strategies continue to be investigated. It is expected that the collective efforts of the biological researchers and pharmaceutical companies will continue to contribute to the development of effective and safe viruses for cancer therapy. Scientists have done the previously unthinkable. Viruses, things that were once a cause of sickness, are now being used to wage warfare against one of the top killers in the world. Medicine is being revolutionized once again as the goals of science are being tested upon and expanded further than ever previously thought. In order to move forward and continue with this promising research, we must continue to probe, dissect and understand the potential that viruses carry.
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