Oncolytic viruses: promising allies in cancer treatment

Oncolytic viruses promising allies in cancer treatment

Viruses, these infectious agents, identified today as “public enemy n ° 1”, also seem able to become allies against cancerous pathologies. This is shown by a group of American scientists who take stock of current research avenues combining classical therapies and genetic engineering.

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The virus oncolytics, literally ” virus cancer cell killer ”, have been known for more than a century thanks to a first case, described in 1904, of a patient suffering from leukemia myeloid in remission after presumably having contracted flu. Whether mutated or wild-type, they have the advantage of replicating preferentially in tumor cells and of leading to their regression by cell lysis and stimulation of the immune response tumor.

The advantages of oncolytic viruses

The cancer cells have very specific features. They produce a lot of nucleotides (to reproduce quickly), they develop a network of blood vessels (oxygenation) and have the ability to deflect the immune response by not responding to certain cytokines (interferon type 1). In addition, they confuse the tracks by producing on their surface protein capable of causinginhibition cells cytotoxic (immune checkpoint). This last point is, moreover, the keystone of research into immunotherapy used in the treatment of certain cancers.

It is these different features which will be exploited in the use of oncolytic viruses. To be a good candidate, the virus used must have little or no toxicity to normal tissues, immunogenic and preferentially target tumor cells.

Through engineering genetic, it is now possible to withdraw Genoa viral (knockout) or to add transgenes (knock-in). These techniques thus make it possible to develop viruses transgenic which will replicate preferentially in malignant cells. The deletion of the thymine kinase which causes the virus to infect highly nucleotide-producing cells, the addition of a gene encoding cytokines stimulating anti-tumor immune activity are just a few examples.

Combination of therapies and genetic engineering

These strategies, which have been under study for several years, still encounter many difficulties. The antiviral pathways of tumor cells are still poorly understood and there are barriers physical decreasing the penetration of the virus into tumor cells. In addition, it can be destroyed by antibody circulating in the body. Nevertheless, a to analyse recent work by American researchers shows that they can be valuable allies, if combined with other therapies classics (radiotherapy, chemotherapy) or more innovative likeimmunotherapy by inhibiting checkpoints (a very promising strategy which only works in 10 to 20% of cases). the genetic engineering applicable to oncolytic viruses, in fact additional weapon vectors through their capacity to generate cell lysis and immune stimulation.

Today four oncolytic viruses are authorized in the world. In the United States and Europe, a virus Herpes simplex (HSV-1) modified has been approved for the treatment of melanoma metastatic inoperable. The myxoma virus (causing myxomatosis in the rabbit), because it has a long genome capable of incorporating stable modifications and, because it is harmless to humans, is under preclinical testing.

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