How Oncolytic Viruses Might Fight Cancer

 by Bianka Anszczak 

(From National Cancer Institute)

Today, ‘viruses’, have been renowned for their negative connotations especially as Coronavirus has been a hot topic for the past 2 years. However, it begs the question, are they all bad? And could they potentially be used for curing diseases, rather than causing them?

Viruses are defined as ‘non-living’ particles. These particles infect our body cells and hijack the cell’s genetic material to make copies of themselves, subsequently spreading to the surrounding uninfected cells. Some viruses such as HBV*, HPV* and HSV*, are known to hold the potential to cause cancers. However, recent research has shown that some of these can be genetically modified to instead prevent infection and formation of these cancers. This is because, they can be easily engineered to have advantageous properties such as: decreasing to ability to infect healthy cells, have power to produce immune-boosting molecules, or even allow them to target and attack tumours that have already formed. These are known as oncolytic viruses, a form of immunotherapy.

So far, there are two main ways in which oncolytic viruses have been found to fight cancer:

1.   Kill cancer cells directly, by infecting them, and then causing them to burst. (This is relatively easy to do as cancer cells usually have impaired antiviral defences making them susceptible to infection).

or

1.   The ‘tell-tale’ markers (antigens), which are released by cancer cells when they die, stimulating an immune response which eliminates the remaining tumour

Now although this sounds promising, thus far there has only been one oncolytic virus therapy approved by the FDA for the treatment of cancer, by the name of T-VEC, which uses a modified version of HSV* to treat melanoma*. However upcoming research makes other treatments such as CAR-T* optimistic too.

CAR-T cells are like a living drug: they find the tumour, are activated, and then expand – just like normal immune cells do during infection. CAR-T works by re-programming and redirecting a patients T-cells, against the malignancy. But how is this done I hear you ask? Simply put, it is done by taking the blood from the patient and separating out the attacker cells (T-cells*), which are then modified by introducing a new gene into the cells, one which encodes a new protein (CAR). This process helps combine the best properties of both B-cells* and T-cells. B-cells help recognise the tumour, and T-cells deploy the domestic police force function, eradicating the cancer cell completely. These cells are then cloned and preserved to run a safety test before they can be administered. To prevent rejection, the patient would be given a low dose of chemotherapy beforehand which is referred to as conditioning. Afterwards, the patients must be closely watched and controlled for immune responses. Eventually, the number of CAR-T cells decreases leaving only a couple by the end, this is incredibly useful as it provides long term protection in case the tumour begins to grow again.

Now although this process sounds simple, researchers still face many challenges. One of the major ones has been identifying the protein that encompasses the entire tumour, as well as the physical barriers that prevent adequate T-cell infiltration.

However, its complexity does not stop researchers which strive to increase its success rate. The main appeal of this type of treatment is the minimal side effects compared to other cancer treatments such as surgery or chemotherapy. 20 years ago, this therapy would have been deemed impossible, so who knows what the future holds.

*HBV – Hepatitis B, causes an infection in the liver

*HPV – Human papillomavirus, has the potential to cause warts

*HSV – Herpes simplex virus, causes genital and oral herpes

*Melanoma – A type of skin cancer

*CAR-T – Chimeric antigen receptor (CAR) T-cell therapy

*T-cells – Patrol around the body, trying to find mutated cells to destroy them

*B-cells – Ability to change and modify their genetic code so that they can recognise different pathogens