Cancer Research Update: Virotherapy

By Genevieve Chan

In your lifetime, you, or someone you know, will be diagnosed with cancer.

Although the mortality rate of cancer in Canada has dropped by 21% in men and 9% in women over the past 20 years, one Canadian is still diagnosed with cancer every three minutes. With billions of dollars invested in cancer research each year, one has to wonder: what answers has research yielded so far? Will we ever discover a cure?

Though not yet a cure, virotherapy has been been a renewed focus for cancer research in the past few years. In virotherapy, cancer cells are targeted by oncolytic viruses – viruses that are either naturally existing or genetically engineered to target tumour cells as the site of replication and destruction, while leaving healthy cells reasonably undamaged.

Viruses are acellular parasites that lack the structures and functions necessary to perform metabolic processes such as energy production, growth or replication. Viruses have simple constructions: they have a protein shell – sometimes surrounded by a lipid envelope – encasing genetic information, either in the form of DNA or RNA.  DNA and RNA differ in size and some molecular components, and RNA viruses tend to be more virulent in human hosts due to their increased ability for genetic mutation.

Due to their simple structure, in order to carry out any metabolic function, the virus must first attach to a host cell and use the host’s capacity for growth and replication. The virus uses the host’s ribosomes and cellular machinery to replicate its genetic information and produce protein shells to encase the new DNA or RNA. The viruses then exit the host cell through lysis (bursting) of the host cell’s membrane, killing the cell.

Given the destructive nature of viruses, our immune systems have developed a strong antiviral response upon entry of the virus. In response to viral infection, the body produces a variety of immune response cells to mark and destroy the infected cells. Virotherapy research focuses on guiding viruses into the body to destroy tumour cells.  In order to do this, researchers need viruses to reach the tumour cells without being recognized and engulfed by the cells of the immune system.

Along with his colleagues, Alan A. Melcher, a British professor of clinical oncology and biotherapy at the Leeds Institute of Molecular Medicine, conducted a clinical study to test virotherapy in human hosts. 10 patients with colorectal cancer were each given an intravenous administration of reovirus, which comes from a family of viruses that usually affect the respiratory and gastrointestinal tracts.

Reovirus is one type of oncolytic virus, with the distinguishing feature of lacking an envelope, or being “naked.”

In the study, Melcher and colleagues discovered that when administered intravenously, some of the naked reoviruses quickly adhered to the circulating white blood cells of the immune system.

This led to the reoviruses acquiring a “stealth phenotype” – instead of being flagged for destruction by the immune system’s antibodies, these reoviruses were carried through the circulation by the white blood cells. When the white blood cells entered the tumour cell beds, the viruses were subsequently released, infecting the tumour cells. Due to the specificity of the reovirus, the surrounding healthy cells were left unharmed.

However, these research results only go so far as to tell us that it is possible for oncolytic viruses to travel undetected by the immune system and become deposited in beds of tumour cells. The actual effectiveness of this type of treatment on cancer cells is still being researched, and its viability as a treatment option is still being explored. Much of the experimentation in this field of research is done on mice, so the extension of these results and theories to human trials is a big step that only a few have begun to take.

There are also many questions that these results raise. Can this type of therapy be applied to the numerous types of cancer with which people are afflicted? Will it have different effects depending on the stage of a patient’s cancer? What are the side effects and associated risks? Will it only control the metastasis and development of tumours, or could it possibly completely rid a patient of cancer? Despite the uncertainties surrounding this ongoing research, these findings have planted a seed for an endeavour with great potential. Just like the first vaccine or the first isolated batch of insulin, hopefully, this will become a breakthrough medical discovery to save countless lives in the years to come.



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