Virotherapy, or using viruses to kill cancer cells

Virotherapy, or using viruses to kill cancer cells

Oncolytic viruses selectively attack and kill cancer cells, which release breakdown metabolites stimulating the immune system to attack remaining tumours; newer 'vaccines' contain tailor-made transgenes that enhance cancer cell death and immune response. 

This article is about another emerging Alternative Cancer Treatment; namely, the use of common viruses to selectively kill cancer cells, leaving healthy cells unharmed. Oncolytic viruses are modified viruses that replicate selectively in tumour cells, but not in healthy cells. They can carry transgenes affecting the tumour microenvironment and causing increased cell death, disruption of blood supplies, and enhanced immune response, according to researchers from the University of Pittsburgh (1).

One company that has already launched a Clinical Trial in the UK, is French Biotech Transgene (2),

Virotherapy and immunotherapy 

There are a number of strategies in, what is now called, virotherapeutics. Technical advances are increasing tumour specificity and replication rates and great advances have been made in the last decade. However, some viruses that replicate well in laboratory tests are much slower in real life situations where cancer tumours erect more barriers (writes former Oxford University Biochemist, Chris Woollams). Hence the need to find ways of enhancing them, even through the patient's own DNA.

Virotherapy has been around for 30 years or more - indeed we even have an article on the successes of their early Virotherapy programme at the MD Anderson Cancer Center in Texas covering a couple of patients with lung cancer, who were given virotherapy in the mid-90s and lived more than 10 years after treatment. 

Early clinical trials showed great potential, but complications emerged - with the immune response and in making the attack stronger and more specific.  

Now, common viruses may be genetically modified to enhance their attack on cancer cells, and/or to prevent harm to healthy cells and/or to overcome cancer tumour barriers and prompt greater immune responses. Although they are most usually referred to as oncolytic viruses (OVs), they are sometimes called cancer vaccines or immune vaccines. Genetic engineering has led to some of these viruses becoming a novel form of gene therapy. They may be modified and tailored to the host's own DNA as with Transgene's myvac®, a viral vector vaccine that is in clinical trials with Ovarian, and Head and Neck cancers (3). Transgene calls it an immunotherapy and claims it has the potential to beat existing PD-1 immunotherapies such as Keytruda and Opdivo.

An explosion in oncolytic virus research

About 12-15 years ago CANCERactive ran a story about researchers lead by Professor Moira Brown in Scotland using the Herpes virus in an attempt to kill brain cancer cells (see Example 9). Her work has progressed and patients have seen extended survival times. Her team believes that the herpes virus could be used to treat many different types of cancer. 

In Cancer Watch, our cancer research centre, we have brought you many more studies. Furthermore, a review on oncolytic viruses in 1920 covered 119 papers and 97 studies, mainly phase 1, between the years 2000 and 2020 (4). Some 20 viruses are currently in clinical trials.

Different viruses, different modifications, use of tailored genetic modifications; this is a really promising area - early oncolytic viruses have now been enhanced to become vaccines and immunotherapy treatments.

There's hardly any line now dividing Dendritic Cell Therapy from Immunotherapy, from oncolytic vaccines.

Oncolytic viruses and vaccines

From Cuba we have a vaccine called CIMAvax, which is an Immunotherapy vaccine for Lung Cancer. 

From Northwestern Memorial Hospital, we have a vaccine for glioma brain cancer, to be used with Avastin.

From Stamford School of Medicine we have a new vaccine that cures lymphoma - it just boosts existing T cells in the tumour tissue and switches them back on to kill the tumour. Scientists are saying it is cancer specific, but can be used with any cancer. It is called localized immunotherapy.

Another example of an oncolytic virus in use was that by Surrey University who reported in 2019 that a strain of the cold virus - the coxsackie virus - when washed through the bladder could knock out bladder cancer cells. 

In 2016, there has been much interest in a non-pathogenic ECHO-7 virotherapy called Rigvir, which has been used to treat melanoma but also a number of other cancers such as breast and prostate cancer. It is not approved for use in America or the UK, even though the development has been through full clinical trials in another EU member state - Latvia. Work was developed in Germany.

Has an oncolytic virus been FDA approved? Yes. One that has been approved by the FDA in the USA is T-VEC, again targeting melanoma. Work is now taking place on other cancers with this Herpes virus.

Another is Reolysin (see example 4 below), know known as Pelareorep. It was fast tracked by the FDA in 2017 for metastatic breast cancer.

Viruses, oncolytic viruses, vaccines - these are alternative cancer treatments of huge potential.

A brief history of oncolytic viruses 

This therapy is not 'there' yet. We do not have the definitive treatment, but it is near. And here is a little history with some examples of what has taken place.

Example 1:     As long ago as 2006 researchers at the Mayo Clinic were testing the use of the Measles virus. We are looking at better ways to treat some of the most lethal cancers, said Dr. Eva Galanis, oncologist and lead researcher on the glioblastoma multiforme project in the measles virus investigation. We have shown in the laboratory and in several animal models that measles virus strains can significantly shrink glioma tumors and prolong animal survival.

This Mayo Clinic work with strains of the measles virus was unique at the time. They called the viruses, vaccines or oncolytic viruses. Early work looked at cancers including glioblastoma multiforme (GBM), recurrent ovarian cancer and multiple myeloma.

By 2015, MD Anderson were treating GBM with a genetically modified common cold virus. Husband and wife researchers Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D. used a cold virus because it doesn't need to be re-engineered much to make it safe for patients and yet it can be used as a seek and destroy missile. They injected very large amounts of the virus straight into the tumour after making a small hole in the cranium. Result: a patient alive and well 4 years later (5).

Example 2:      Dr. Kevin Harrington, working at The Royal Marsden Hospital, London for the Institute of Cancer Research, studied 17 patients found that use of the Herpes virus with chemotherapy and radiotherapy can help kill cancer cells in most patients. It does this in three ways: By direct attack on the cancer cells, multiplying inside them; the genetic modification is designed to produce a protein to activate the immune system; the virus itself causes a rapid increase in the immune system against it (and the cancer cells it is living in).

The treatment was most effective with early stage cancers - the study was with cancers of the head and neck area. 93% showed no recurrence of cancer after surgery and 82% of patients still did not show any recurrence of the disease more than two years later.

The herpes virus is genetically manipulated so that it attacks and thrives in cancer cells but cannot infect healthy cells.

The worry, of course, is that the genetically modified virus does cause health problems years later, maybe even to the population at large. (August 2010; Journal of Clinical Cancer Research). 

Example 3:     Researchers at Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center, are conducting a clinical trial using the Reovirus. Normally, you have experienced this virus at least once by the age of 5, causing coughing and diarrhea, but sometimes no symptoms. Apparently, the researchers found that the virus grows like gangbusters inside cancer cells, because of a specific attribute of a cancer cell, namely that the Ras gene is dominant and making it divide paridly. In healthy cells the p53 gene suppresses the Ras gene. Researchers are currently conducting a Phase II Clinical Trial with small cell lung cancer patients. Again, the virus has been genetically modified to prevent harm to healthy cells.

Example 4:      Drugs can be made from the virus: Researchers at Oncolytics Biotech Inc., of Calgary, Canada, have developed a therapeutic drug, Reolysin, from the same Reovirus and are conducting multicenter clinical trials for a variety of cancers. Their website claims that 'the FDA has recently granted fast track approval (but the link doesn't work!). Reolysin, which is now known as PALAREOREP, was always used in conjunction with other treatments, across cancers from breast to ovarian and pancreatic.

Renowned American Hospital Cedars-Sinai is one of those participating in the trials, and in this case is looking into recurrent gliomas, the most common and deadly brain cancer. "Although not every glioma cell line has an activated Ras pathway, Ras activation is very common in these malignant brain cancers. In lab tests and animal studies, the reovirus appears to target Ras-activated tumor cells and leave normal cells alone," said a spokesperson from Cedars-Sinai.

Example 5:     In Sptember 2009 Dalhousie Medical School have proven that Reovirus can infect and kill breast cancer stem cells (6). This breakthrough finding was published in Molecular Therapy, the journal of the American Society of Gene Therapy.

Dr Lee, head researcher said, It is only within the past few years that the scientific community has understood the full significance of cancer stem cells and the urgent need to find a means of eliminating them (Ed: Actually, UK embryologist John Beard in 1906 told the world but his work was ignored until picked up by William Kelley then Dr Gonzalez from the 1970s. Oh, but they really were Alternative Doctors!)

Cancer stem cells are essentially mother cells, explains Dr. Lee, Cameron Chair in Basic Cancer Research at Dalhousie Medical School. They continuously produce new cancer cells, aggressively forming tumours even when there are only a few of them.

Cancer stem cells are difficult to kill as they respond poorly to chemotherapy and radiation. As Dr. Lee notes, You can kill all the regular cancer cells in a tumour, but as long as there are cancer stem cells present, disease will recur. Dr. Lee is optimistic that his team has found the key to destroying cancer stem cells.

Example 6:     Boston University School of Medicine (BUSM) presented their findings in the Journal of Virology on December 2010. They were using a virus, vesicular stomatitis virus (VSV), to kill cancer cells. VSV is supposedly not an important cause of ill health in humans.

In cancer cells a major signaling pathway, called the AKT signaling pathway, is frequently turned on and AKT signaling is a cell survival signal, helping to keep the cancer cells alive. VSV can switch off the AKT pathway and cause cancer cell death. VSV can also prompt the immune system to produce interferon which also targets the diseased cancer cell.

Example 7:      At Memorial Sloan Kettering Cancer Center in New York, May 2011, Joyce Wong M.D. published findings looking at oncolytic viruses to infect cancer cells, and especially stem cancer cells in pancreatic cancers. Results showed that there was the potential to do this, a very important finding.

Example 8:      Viruses can also be genetically modified to be carriers. For example: In December 2009, (Molecular Therapy) Ohio State University researchers looked at modifying viruses so that they carried a gene which could block tumour blood cell formation.

With brain tumours, research leader Balveen Kaur, associate professor of neurological surgery said, "This is the first study to report the effects of 'vasculostatin' delivery into established tumors, and it supports further development of this novel virus as a possible cancer treatment. This study shows the potential of combining an oncolytic virus with a natural blood-vessel growth inhibitor such as vasculostatin. Future studies will reveal the potential for safety and efficacy when used in combination with chemotherapy and radiation therapy," she says.

The work still needs to be trialled with humans. In this study researchers injected the cancer-killing virus, called RAMBO (for Rapid Antiangiogenesis Mediated By Oncolytic virus), directly into human glioblastoma tumors growing either under the skin or in the brains of mice.

Example 9:        Professor Norman Nevin, chair of the UK gene therapy committee believes the UK is at the forefront of oncolytic virus work. For example, his committee gave the go-ahead several years ago for a team at Glasgow University (Southern General Hospital), lead by Professor Moira Brown, to treat 100 patients with gliomas using a genetically modified form of the herpes virus. Here initial findings and the development work has been covered in Cancer Watch in October 2013 (see HERE).

Our Bottom Line on oncolytic viruses

In 2021 there was a review by researchers in Holland on GBM (brain cancer) and oncolytic viruses. It talked about impressive results to date in a few subjects, but work was still needed to find Biomarkers for a better response. Perhaps that is a fair summary of where Oncolytic viruses are in 2021. Nearly there but could do better (7).

As always, we are not endorsing, writing in glowing terms, or promoting. At CANCERactive, we just call it honestly as we see it. And clearly there is definitely work of great potential going on here. Hopefully this briefing, on a subject that has grown rapidly in the last few years, will help you to make more informed choices on your options for cancer treatment over the coming years, should you be offered virotherapy, vaccines or oncolytic viruses as a therapy..



  1. Transgene France -

  2. Oncolytic virotherapy and tumour microenvironmrent; Adv Exp Med Biol; 2017;1036:157-172, Sarah E. Berkey, Steve H. Thorne, David L. Bartlett -

  3. Transgene Clinical Trials - 

  4. Clinical Landscape of Oncolytic virus research in 2020; Nicholas Macedeno et al; J Immunother Cancer. 2020; 8(2):

  5. Unleashing the cold virus to kill cancer -

  6. Dalhousie Medical School, Reovirus infects and kills breast cancer stem cells -

  7. Personalising Oncolytic Virotherapy for Glioblastoma; Cancers (Basel). 2021 Feb; 13(4): 614. -


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