Oncolytic Viruses: Future Of Cancer Therapy?

The term “oncolytic viruses” refers to the modified viruses that are able to selectively infect and destroy cancer cells in the body. The idea is wonderful. The exciting part is that, in theory, there are no principal problems that could prevent the development of such technology. But can it be done in practice?

Not so many years ago, this rather specialized scientific topic suddenly became a subject of broad public debates. Hollywood’s blockbuster I am Legend graphically depicted how humankind turned into blood-thirsty monsters, thanks to the newly developed virus-based anticancer therapy. In this cinematographic scenario, very soon after the therapy was introduced the virus mutated with the most lethal consequences imaginable.

Good movie (and this one was good, at least well made) does increase the public awareness about the dangerous toys the scientists out there might be playing with. Unfortunately, it is extremely unlikely that any viral therapy would be as effective in curing cancer as the movie suggested. On the positive side, it’s even more unlikely that such therapy would lead to global pandemic of vampirism.

The idea of using viruses to treat cancer is not new

The idea exists for at least a century, actually. Since the early 1800s there have been frequent reports of correlation between viral infection and tumor shrinkage. There was, for instance, a classic example of 42 year old woman who was suffering from myelogenous leukaemia. Her disease went into remissions after she contracted influenza. This and other observations were not properly investigated at the time. As a matter of fact, biomedical science has reached the level of development sufficient for proper investigation of such cases only in the second half of the last century.

How oncolytic viruses recognize cancer?

But how oncolytic viruses create this distinction between the normal and cancerous cells? Generally when any virus infects a host, it hijacks the cellular machinery and makes it to produce more viruses. A number of virus-induced changes are very similar to the conditions required for the growth and proliferation of the tumor cells. As a result, viruses prefer to infect cancer cells.

More robust and more cancer-selective viruses can be made through genetic engineering. These viruses, ideally, would ignore healthy cells of the host altogether. Potential candidates for such genetic manipulations include Adenovirus, Herpes Simplex Virus (HSV), Vaccinia virus, Polio virus and Influenza virus.  

In addition to their ability to recognise cancer cells, oncolytic viruses also produce an immuno-stimulating effect on the recipient. Virus-modified cells get recognized and eliminated by immune system thus further promoting elimination of tumor.

Oncolytic viral therapy is promising but faces significant challenges

Any attempt to implement viral therapy for cancer treatments has to solve multiple practical problems. One of them is the problem of immunological response to the virus. Preexisting immunity against the commonly encountered viruses like vaccinia or influenza limits their use. Similarly, the small pox eradication program has resulted in the presence of antibodies against this virus in a wide section of population.  

Another problems are insufficient specificity in the uptake of the viruses by cancer tissues, and their low stability in the blood stream. In order to bring about an effective outcome, the virus must persist long enough within the circulation without being degraded or depleted and at the same time target the cancer cells selectively.

Reduction in systemic availability of many invading viruses can be caused by normal function of spleen, lungs and liver. These organs can filter the virus from the blood. In addition, human erythrocytes bind the viruses on the cell surface.  This further reduces the availability of viral particles to infect tumor cells.

Fast growing tumors are known to have a chaotic and underdeveloped system of blood vessels. This is another factor complicating the delivery of oncolytic viruses. Direct injection of viruses into tumor may help in solving this problem.

In addition to these purely scientific and technical problems, the research work in this direction is chronically underfunded. At the same time, any work with viruses is heavily regulated, and multiple approvals are needed to meet the growing number of safety guidelines.

Current state of affairs: What’s in store for the future?

The naturally occurring viruses are not good enough to withstand the rigors of the human immune system. Therefore, the next generation of oncolytic viruses needs to be engineered from the pathogenic forms. The recent boom in the field of genetic engineering has made it possible to selectively delete viral genes that might be needed for the infection of healthy cells but are quite dispensable in case of the cancer targets.

A number of viruses, such as Adenovirus, Herpes Simplex Virus, Vaccinia Virus, and Influenza Virus were modified in this way. Artificial carrier microspheres and vesicles can also be utilized to avoid the hostile environment and alleviate the immunologic barriers faced by the oncolytic viruses.

Researchers in clinical trials have previously reported a significant improvement in the response of the patients to usual chemotherapy and immune-modulators when they were used alongside the oncolytic virus therapy.

The idea of using viruses to destroy cancer cells selectively looks very attractive. Despite some early positive reports, lots of research still need to be done to see if this approach can really make a difference.