The application of oncolytic viruses in tumor therapy

Onkolitički virusi su definirani kao virusni soj koji ciljano inficira i ubija stanice rake, ali ne inficira benigne stanice. Ovo svojstvo ih čini primjenjivim u tumorskoj terapiji, i pomoću tehnika genetskog inženjerstva je konstruirano mnoštvo sojeva onkolitičkih virusa koji specifično ciljaju različite vrste tumora. Divlji tipovi virusi se mogu modificirati za specifično inficiranje stanica raka delecijom određenih virusnih gena, kontrolom transkripcije virusnog genoma pomoću tkivno-specifičnih promotora ili microRNA, i mijenjanjem virusnih receptora i fuzijskih proteina. Osim što izazivaju citotoksičnu lizu i tako ubijaju maligne stanice, onkolitički virusi također pridonose razvoju dugotrajnog adaptivnog imunosnog odgovora oslobođenjem PAMP-ova, DAMP-ova, i tumor specifičnih antigena iz stanica raka. Također se mogu umetnuti razni transgeni u genome onkolitičkih virusa, što omogućuje primjenu različitih strategija u tumorskoj viroterapiji i pojačava učinak same viroterapije. Na primjer, imunoterapija se može provesti pomoću onkolitičkih virusa tako da se umetne gen za citokin u onkolitički virusni vektor, a kemoterapija se kombinira s viroterapijom tako da se umetne gen za konvertazu prolijeka u virusni vektor. Prva obrada onkolitičkim virusima je odobren u Sjedinjenim američkim državama 2016. godine, i očekuje se da će nakon ovog uspjeha sve brže dolaziti novi onkolitički virusi na tržište. I uz sve prednosti upotrebe onkolitičkih virusa u tumorskoj terapiji, i dalje se intenzivno radi na tome da im se poboljša klinička učinkovitost.Oncolytic viruses are defined as viral strains that selectively infect and kill cancer cells, and do not infect non-malignant cells. This characteristic makes them applicable to cancer therapy, and with the help of genetic engineering numerous strains of oncolytic viruses have been constructed to target a wide variety of different tumors. Wild type viruses can be modified to specifically target cancer cells by deleting certain essential viral genes, by controlling transcription of the viral genome with the help of tissue-specific promoters or microRNAs, and by changing viral receptors and membrane fusion proteins. In addition to killing tumor cells through direct cytotoxic lysis, oncolytic viruses also contribute to the development of a long-term adaptive immune response through the release of PAMPs, DAMPs, and tumor-associated antigens from cancer cells. Various transgenes can also be inserted into the genome of oncolytic viruses, which allows different cancer therapies to be used in conjunction with virotherapy. For example, immunotherapy can be carried out with the help of oncolytic viruses by inserting a cytokine-coding gene into an oncolytic virus vector, and chemotherapy can be combined with virotherapy by inserting a gene encoding for a prodrug convertase into a viral vector. The first treatment utilizing oncolytic viruses was approved in the United States in 2016, and after this success it is expected that more oncolytic viruses will rapidly arrive on the market. Even with all the benefits of using oncolytic viruses in cancer therapy, there is still much work to be done to improve their clinical efficacy