Oncolytic Viruses - The Powerful New Therapeutic Agents In Cancer Therapy
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Oncolytic Viruses To Kill Cancer Cells – Game Changer In Cancer Therapy

Getting rid of cancer cells is tricky. It’s like a game where you are told to burst green and purple balloons from a group of red, purple, yellow, and green ones. And every time you burst a green or purple balloon, two more balloons of the same kind appear. You are tempted to burst the balloons randomly, but if you do so, you will burst red and yellow balloons, which could be dangerous.

Cancer therapy is tricky because the green and purple balloons are the cancer cells, and red and yellow balloons represent healthy cells, and one has to make sure that the therapy is not killing or damaging healthy cells.

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A survey conducted in more than 1,000 cancer patients by ICR reveals that over one-third of the surviving patients have received state-of-the-art targeted drug treatment or immunotherapy.

Patients are now looking for kinder, smarter treatments, and not the aggressive chemotherapies.

Immune checkpoint inhibitors

When it comes to cancer therapies, Immune checkpoint inhibitors are used to selectively kill cancer cells. Usually the body’s immune cells are blindfolded against cancer cells due to some signals sent out by cancer cells to keep the immune cells away. Basically, the immune cells don’t recognize cancer cells as foreign substances.

The immune checkpoint inhibitors remove the blindfold from the immune cells so that they can recognize and attack cancer cells. These therapies were hugely successful, but only certain patients whose cancer cells are immunologically “hot,” and they have lots of immune cells in the vicinity of cancer cells to take action responded to the therapy.

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Oncolytic Viruses and Immune checkpoint inhibitors

A new virus called oncolytic virus is trending in cancer research now. They are viruses that can kill cancer cells as well as draw the attention of immune cells to cancer cells.

Professor Kevin Harrington, Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust and Professor of Biological Cancer Therapies at the ICR, is now looking for ways that the virus can kill cancer cells and spark the immune system into action against tumors.

Nature Reviews Drug Discovery recently published his review on the optimization of oncolytic virotherapy in cancer treatment.

Oncolytic viruses can kill cancer cells through the process of lysis, just like the way a common cold virus invades the cell, reproduce, and then bursts the cell releasing thousands of its copies. And this bursting alerts the immune cells that something is wrong, attracting immune cells to cancer cells, not affecting the healthy cells.

A protein called PD-1 when binds to another molecule called PD-L1 masks the cells from immune cells. The immune checkpoint inhibitors block these molecules so that the immune cells can recognize and attack tumor cells. Oncolytic viruses encourage cells to produce more of these molecules, increasing the possibility of immune checkpoint inhibitors binding to the cancer cells.

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This is a great help for patients whose tumors have developed resistance to immune checkpoint inhibitors. The oncolytic viruses reverse the resistance telling the cancer cells to produce more of the molecules the drugs act on.

This new combination of oncolytic viruses with immune checkpoint inhibitors increases the number of patients who can benefit from immunotherapy.

This shows the high potential of oncolytic viruses in cancer treatment as they can not only kill cancer cells but also encourage the immune system o attack cancer cells.

Since viruses are small and easy to manipulate, scientists can engineer the genetic material of the virus so that they can easily get inside of cancer cells.

Also, they can engineer the oncolytic viruses to have sequences corresponding to microRNAs present in healthy cells. If the virus invades a healthy cell, the microRNA present in the cell will bind to the specific sequence in the virus, preventing any protein production by the virus, thus protecting healthy cells from the virus.

On the other hand, cancer cells don’t contain the matching microRNA molecule for the sequence in the virus, so the virus can reproduce itself freely inside those cells. This will reduce the chance of healthy cells being affected by the virus and increases the effect in tumor cells.

Oncolytic Viruses and CAR-T cell therapy

CAR-T cell therapy or chimeric antigen receptor T-cells are the main attraction of modern, targeted cancer therapy. Immune cells are harvested from a patient and engineered to find specific molecules on the surface of the patient’s tumor and re-administering them to the patient.

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But sometimes, the engineered immune cells are not able to get to the tumor cells due to the tumor’s microenvironment. This microenvironment consists of the extracellular matrix, a network of cells and collagen and other molecules that shield the immune cells from getting closer to the tumor cells. This is especially bad in pancreatic cancer.

Oncolytic viruses can help the engineered immune cells to reach the tumor cells. The viruses can be engineered to contain a gene that would blast through the extracellular matrix, paving a path for the immune cells to reach tumor cells.

Although a lot of research is required on oncolytic viruses, they hold a huge hope. Talimogene laherparepvec or T-VEC is the only oncolytic virus approved for use in the US and Europe and is approved to be used only in advanced-stage melanoma.

The ICR and Royal Marsden played were involved in phase I, II, and III clinical trials of T-VEC.  Professor Kevin Harrington was invited for the NICE and EMA hearings that led to the approval of T-VEC in Europe.

They could go a long way towards benefiting a large, currently under-served population of patients whose cancers need a push to respond to cutting-edge treatments like immune checkpoint inhibition.