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.