Definition of An Oncolytic Virus
Introduction
An oncolytic virus is a form of promising therapeutic tool for the treatment of malignant tumors, which uses viruses to selectively infect and kill tumor cells and further to induce or boost specific antitumor immunity. At the beginning of the 20th century, physicians observed that patients with cancer experienced partial tumor regression after natural viral infections, which showed that these viruses could be used for cancer cell therapy that was vulnerable to viral infections. However, many critical factors, such as the safety concerns of using oncolytic viruses and the lack of tools to manipulate viruses, have hindered research in the development of oncolytic virus therapy.
Recently, the development of molecular biotechnology allows modifications of viral genomes genetically and optimizes the transformation of available viruses with weak pathogenicity. These methods are used to enhance the oncolytic effect and reduce adverse reactions to maximize both efficacy and safety. Indeed, the oncolytic virus can stimulate a pro-inflammatory tumor environment by enhancing antigen recognition and robust immune responses. It overcomes the immune evasiveness and escape of malignant cells to eliminate the tumor cells.
Fig.1 Diversity of oncolytic viruses and their modes of action. (Ungerechts, 2016)
Unique Features of Oncolytic Virus
The increasing interest of oncolytic virus therapy relies on its advantageous features:
(a) The oncolytic virus replicates explicitly in a tumor-selective manner and is non-pathogenic.
(b) The oncolytic virus targets multiple oncogenic pathways and applies multiple means for cytotoxicity.
(c) The oncolytic virus has strong stimulating effects on immune cells infiltrating the tumor tissue, which can significantly alter the nearby tumor microenvironment.
(d) The oncolytic virus triggers the expression of pro-inflammatory and immuno-stimulatory cytokines, resulting in the activation of strong immune responses.
Different types of Oncolytic Viruses
Currently, numerous types of oncolytic viruses are used as therapeutic agents in different stages of investigation for cancer therapy, including both genetically engineered oncolytic viruses and naturally occurring oncolytic viruses. Mutation and/or lack of specific virus genes to put the essential genes of the virus under tumor-specific and/or tissue-specific gene promoters so that the expression of crucial virus genes is restricted in tumor cells to improve safety. Disease-specific oncolytic viruses used in recent research include adenovirus, herpes virus, reovirus, Newcastle disease, measles virus, Coxsackie, and varicella virus. In addition, much-existing results of some large prospective clinical trials show that clinical symptoms in patients have been relieved after infection with the viruses, providing essential evidence into further clinical studies. Oncolytic viruses have acceptable safety with minimal serious adverse events reported. Therefore, the oncolytic virus is a promising tool that brings a multi-mechanistic approach and an acceptable safety profile to patients.
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Reference
- Ungerechts, G.; et al. Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses. Molecular Therapy-Methods & Clinical Development. 2016, 3:16018.