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Introduction
Cancer ranks among the top reasons for mortality globally, being the cause of one in six deaths. Breast, lung, colon rectum, and prostate cancers are the most common cancers recorded worldwide. It can develop anywhere in the body and is named after the location where the abnormal proliferation of cells was first detected. Research has been ongoing to find out a novel solution for this deadly condition. Experts have discovered that using oncolytic viruses helps manage the condition. This article deals with using oncolytic viruses to manage tumors.
What Are Oncolytic Virus?
Viruses are foreign bodies that enter the human body and cause viral infections. After entering the body, it copies the genetic makeup of the body and uses it to replicate itself, making copies of itself. Subsequently, they infect the adjacent normal cells. Certain viral infections have been associated with the development of certain types of cancers, like the hepatitis B virus in liver cancer and the human papillomavirus (HPV) in cervical and head and neck cancers. Studies have also have found that taking HPV vaccines has been associated with reducing the risk of cervical cancer in young women, in addition to preventing HPV infections.
Recent research has helped develop viruses targeted to attack tumor cells. Most of these viruses are modified genetically and are called oncolytic viruses. Developing oncolytic viruses has been a rewarding and promising approach to cancer research. The benefits of oncolytic virus therapy include:
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The immunodeficiency of cancer cells frequently results in compromised antiviral defenses.
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These viruses can be modified to confer specific therapeutic benefits, like reducing their ability to infect normal cells or to release immune-boosting chemicals after they infect tumor cells and to produce chemicals that can boost immunity.
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Oncolytic viruses also kill cancer cells after infecting them, releasing cancer antigens. These antigens can then trigger the immune system to locate and eradicate any tumor cells that may still be present in that area or elsewhere in the body.
How Does Oncolytic Virotherapy Work?
The direct lysis of tumor cells (direct oncolytic activity) is oncolytic viruses' initial mechanism of action. These viruses also have the ability to cause the immune system to produce anti-tumor immunity, causing their lysis. These oncolytic viruses release tumor antigens that cause an anti-inflammatory response, resulting in the death of the tumor cells.
Tumor-Selective Infection, Replication, and Oncolysis: Several factors drive tumor selectivity in oncolytic virotherapy. The first method is to enter the cells through specific receptors. Oncolytic MV-specific identification is mediated by the expression of SLAM/CD150 and CD46 receptors on tumor cells. The mutation of surface proteins helps to recognize specific receptors that enter the tumor cells. Retargeting oncolytic viruses to tumor-associated receptors, such as the epidermal growth factor receptor (EGFR), promotes more effective infection and enhanced viral replication.
The next method is that tumor cells replicate faster than normal quiescent cells. Hence, the oncolytic virus uses the genetic makeup of normal cells to replicate. Modifying these viruses genetically to remove the unnecessary virulent genes and insert tumor-specific promoters promoted the activity of oncolytic viruses.
Thirdly, the immune response in tumor cells is disrupted. Lesser type I interferon (IFN) signaling blocks viral clearance. However, normal human cells produce IFN and limit virus replication in the body. As a result, the oncolytic virus does not destroy healthy cells. Nevertheless, the role of IFN in causing antiviral effects is still debated.
After cell lysis, the oncolytic virus spreads to nearby areas, destroying the tumor cells. The ability of the virus depends on the type and nature of the virus and the tumor’s susceptibility to cell death. Increased lysis by the oncolytic virus may also harm normal, healthy cells.
Systemic Anti-tumor Effect: After replication, the oncolytic virus induces cell death in the tumor cells. This occurs mainly through releasing danger-associated molecular pattern signals (DAMPs) and tumor-associated antigens (TAAs). This facilitates the removal of viable neoplastic cells. Innate immunity and tumor-specific adaptive anti-tumor responses further eradicate the neoplastic cells.
How Are Oncolytic Viruses Administered?
The success of oncovirus-based immunotherapy depends on the appropriate mode of administration. Injecting the oncolytic virus into a single tumor site can cause it to be directly targeted at the neoplastic cells. However, its application in this way has a limited effect on metastatic tumors. Systemic injection is more effective in metastatic tumors. However, it gets eliminated from the circulation faster, even before reaching the tumor site in some cases. Carriers, like transformed tumor cells, immune cells, and stem cells, have been used to administer oncolytic viruses to the target sites. Different routes of administration like intraperitoneal (IP), subcutaneous (SC), intracranial (IC), intramuscular (IM), intranasal, intravesical (IVE), aerosol, and inhalation have been tried during clinical and pre-clinical trials.
What Are the Current Challenges in Using Oncolytic Viruses?
Despite the potential of oncolytic viruses in anti-cancer therapy, there are some limitations that they currently face before they are widely used in cancer therapy. These limitations include inadequate penetration of the oncolytic viruses, the host's antiviral immunity, the patient's selection, and low efficacy when used alone. More research is required to clarify these limitations and to use oncolytic viruses as an anticancer agent.
Can Oncolytic Viruses Be Combined With Other Treatment Options?
Oncolytic viruses have been found to be more useful and effective when used in combination with other cancer treatment options. This is especially true when used as a single agent when its efficacy is still low. Hence, they can be potent partners with other therapies.
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Radiotherapy and Oncolytic Viruses: Oncolytic viruses can function well as radiosensitizers (an agent that enhances the anti-cancer effect). When combined with radionuclide therapy, NIS-armed oncolytic VSV demonstrated high IT viral replication, which in subcutaneous or orthotropic mouse tumor models led to improved tumor shrinkage and extended life.
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Chemotherapy and Oncolytic Viruses: Chemotherapy can improve oncolytic virotherapy by helping the oncolytic viruses evade antiviral immune responses; this makes combining chemotherapy with oncolytic viruses an alternative to cancer immunotherapy.
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Targeted Small Molecular Agents and Oncolytic Viruses: In multiple preclinical investigations, the FDA-approved medication Ruxolitinib, a selective JAK-1/2 inhibitor, increased the activity of multiple oncolytic viruses by blocking antiviral JAK/STAT signaling. No adverse reactions were seen.
Conclusion
In cancer treatment, oncolytic viruses are potent novel therapeutic agents. Since oncolytic viruses are widely thought to have direct oncolysis and cancer immunological effects, they have gained increasing attention in the twenty-first century. It is vital to know about the safety and potential side effects of this therapy, though, as a successful cancer treatment should target the tumor, encourage regression, and cause the least amount of systemic side effects.
