The role of oncolytic viruses in cancer therapy
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Mobarakeh Ajam-Hosseini,1 Amir Atashi,2,* Zahra-sadat Mousavi,3
1. Department of Cell and Molecular Biology, Faculty of Basic Sciences, Kharazmi University
2. Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Shahroud University of Medical Sciences
3. Student Research Committee, School of Allied Medical Sciences, Shahroud University of Medical Sciences
- Introduction: Oncolytic viruses (OVs) are described as genetically engineered or natural viruses that are used to treat a variety of cancers, especially in advanced stages. OVs selectively proliferate in cancer cells without damaging normal tissues and lead to tumor regression by inducing a host anti-tumor immune response.
In general, viruses provide a unique host for cancer treatment by facilitating genomic manipulation to increase viral tropism in neoplastic cells, increase selective proliferation, modify viral pathogenesis, and induce antitumor immunity. In addition, genetic engineering of additional genes to enhance anti-tumor immunity, increase the sensitivity of tumor cells to ionizing radiation and ultimately increase patient immunity can be considered as the main and important characteristics of oncolytic viruses.
Among the various viruses, including adenovirus, herpesvirus, poxviruses, coxsackie A virus, Newcastle disease virus, reovirus, picornavirus, and vaccinia virus, that have been developed for the treatment of oncolytic diseases, the most common OVs used in clinical trials are adenovirus, HSV-1, reovirus, picornavirus, and poxviruses.
- Methods: An overview of the organized literature was conducted in the PubMed database. Out of 4120 articles from 2000 to 2022, articles related to the role of Oncolytic viruses in cancer treatment were screened and studied.
- Results: Worldwide, three OVs have been approved for the treatment of advanced cancers. The first is Rigvir, an RNA virus derived from the ECHO-7 picornavirus strain. Then, a genetically modified adenovirus called H101 was approved for the treatment of nasopharyngeal carcinoma in combination with cytotoxic chemotherapy. Finally, Talimogene laherparepvec (T-VEC), an attenuated herpes simplex virus type 1 (HSV-1), was approved in 2015 by the US Food and Drug Administration for the treatment of melanoma patients. Currently, T- VEC is used in many clinical trials.
Genetic manipulation has occurred in the HSV-1 genome in order to selectively replicate the virus in cancer cells, attenuate pathogenesis, and enhance the host antitumor immune response. For this purpose, deletion of ɣ34.5 and ἀ47 genes can be mentioned, which the ɣ34.5 gene prevents from stopping the protein synthesis of host cells during viral infection. Therefore, by deleting this gene, the virus cannot replicate in normal cells, and on the other hand, by inhibiting the reduction of MHC class I expression, the immune response against cancer cells is increased. Deletion of the ἀ47 gene also leads to early expression of the US11 gene and increase in viral replication in cancer cells. Another important change in HSV-1 is the placement of a transgene called GM-CSF at the ɣ34.5 deletion site. GM-CSF is a human macrophage granulocyte colony stimulating factor that is thought to aid in the uptake and maturation of dendritic cells and ultimately lead to the production of immune stimuli.
One of the important issues in the clinical development of OVs is choosing how to present the virus to the cancer patient. In early studies, the direct intratumoral (IT) injection was used, which may be challenging for visceral and central nervous system (CNS) tumors. Another strategy is intravenous injection, which seems simple and can target multiple metastatic areas, but may be complicated by rapid dilution in the circulation, neutralization by antiviral antibodies and other serum proteins. It should be noted that the most common side effects of OVs are fever, fatigue, chills, nausea / vomiting, flu symptoms, low pain at the injection site, and other common side effects, all of which have low-grade symptoms.
Most studies of cancer treatment with OVs are monotherapy, but there are studies based on combination therapy. Contrary to expectations, most combined studies were in the form of OV evaluation and cytotoxic chemotherapy, while treatment of OVs and immunotherapy has received less research.
- Conclusion: Although significant progress has been made to date in the development of oncolytic viruses as a treatment for cancer, but further research is needed to optimally select viruses, describe the clinical effects of OVs, how the virus is delivered to the tumor site, and immunogenicity. However, there is growing evidence that this approach is potentially promising for the treatment of human cancers
- Keywords: Oncolytic virus, Tumors, cancer therapy, Herpes simplex virus type 1, Adenovirus
