Oncolytic virotherapy is an emerging treatment modality which uses replication competent viruses to destroy cancer. Oncolytic viruses selectively infect and damage cancerous tissues without causing harm to normal tissues. Many, if not most, naturally occurring viruses have a preferential, although non-exclusive, tropism for tumours and tumour cells.
Oncolytic viruses can kill infected cancer cells in many ways, ranging from direct virus-mediated cytotoxicity through a variety of cytotoxic immune effector mechanisms. Following viral replication oncolytic viruses induce cell death, which can directly eliminate viable tumour cells, but also set the stage for initiating systemic immune responses.
Cancer cells have evolved sophisticated strategies for avoiding immune-mediated destruction. Tumour cells and the microenvironment can express immune-inhibitory surface receptors that inactivate effector immune cells, and secrete factors that facilitate the recruitment of immune-suppressive cells, such as tumour-associated macrophages and myeloid-derived suppressor cells, to sites of tumour growth. Oncolytic viruses modify this suppressive micro-environment. These changes promote immune-mediated tumour cell recognition and eradication. Thus, virotherapy mobilizes the natural defences of the immune system against foreign genetic information that has entered the body and at the same time also against genetically modified cells and tissues, including malignant cells.
Some oncolytic viruses have recently been shown to be capable of destroying cells that are typically resistant to conventional chemotherapy and/or radiation. Therefore, oncolytic virotherapy is of special importance for chemotherapy-resistant tumours, like melanoma. Oncolytic viruses could be used both as monotherapy and in complex with other therapies. Besides, compared to cytotoxic and radiation therapy, tumour cell break-down products are eliminated much faster after virotherapy.
The principal target of oncolytic viruses is similarly to that of radiotherapy and chemotherapy – a cancer cell.
Oncolytic virotherapy differs from conventional and even targeted treatments in several essential advantages:
- it is highly selective and able preferentially seek and enter tumour cells while sparing non-cancerous tissues and cells;
- so far, no resistance has been evaluated during oncolytic virotherapy;
- it stimulates natural defence system of the body by activating immunity, which other treatment methods usually suppress;
- it is maximally efficient in replicating inside cancer cells and destroying tumour tissue;
- it is well tolerated having minimal side-effects in cancer patients, and even more importantly – oncolytic viruses are non-pathogenic in humans;
- it carries little to no risk of genomic integration as viruses do not integrate into the host cell DNA (replicates only in cytoplasm) and therefore no risk of mutation;
- it can be applied for tumours that are not sensitive to radiotherapy and chemotherapy like melanoma;
- it can be used in various treatment phases: before or after the surgery or in between radiotherapy or chemotherapy sessions;
- it could be administered both locally (directly into the tumour tissue or closely around it) and systematically.
It may take a longer period of time for oncolytic virotherapy to start expressing it’s activity. Thus, the conventional response assessing criteria may differ from those for conventional chemotherapy as it works quicker. Sometimes a pseudo-progression may be observed in the very beginning of treatment due to infiltration of tumour tissue with lymphocytes. Therefore the response should be checked after another time period.
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