The Viral Knock: Using the Oncolytic Newcastle Disease Virus to Improve Cancer Treatment

Anshik Pathak^*
*Correspondence: Anshik Pathak, Department of Oncology, Reliance Foundation Hospital and Research Centre, Mumbai, India, Email:

Keywords

Cancer • Radiation • Treatment • Virotherapy

Introduction

One of the most promising candidates in oncolytic virotherapy is the Newcastle Disease Virus (NDV). NDV, a naturally occurring avian paramyxovirus, has shown remarkable oncolytic potential against various cancer types. Its ability to infect and selectively replicate within tumor cells, leading to their destruction, has garnered attention in the scientific community. Moreover, NDV elicits an immune response, further augmenting its therapeutic efficacy. In this review, we delve into the biology of NDV, its mechanisms of action, and the current state of research, aiming to demonstrate the transformative potential of this viral warrior in the battle against cancer. NDV is an enveloped, negative-sense, single-stranded RNA virus belonging to the paramyxoviridae family. While it is mostly known for its devastating impact on avian populations, researchers have discovered its unique oncolytic properties in mammalian cells, making it an attractive candidate for cancer therapy. NDV is characterized by its high genetic diversity, allowing it to infect various types of cancer cells, including breast, prostate, lung, and pancreatic cancers, among others. NDV exploits multiple mechanisms to target and destroy cancer cells, distinguishing it from conventional therapies. Firstly, it possesses a natural tropism for tumor cells due to their overexpression of specific surface receptors, such as the sialic acid residues, which NDV recognizes and binds to. Subsequently, NDV gains entry into the cancer cells through endocytosis [1].

Despite the promising results, oncolytic virotherapy, including NDVbased treatments, still faces several challenges. One major concern is the development of antiviral immunity in patients, which could hinder the effectiveness of repeated treatments. Strategies to mitigate this issue include combining NDV with immune checkpoint inhibitors or other immunomodulatory agents. Another challenge lies in optimizing viral delivery and distribution within the tumor microenvironment. Factors such as the extracellular matrix and immune response within the tumor can limit viral spread. Researchers are actively exploring ways to enhance viral penetration and persistence within the tumor to maximize therapeutic efficacy. Oncolytic virotherapy, with the Oncolytic Newcastle Disease Virus at its forefront, represents a promising avenue in cancer treatment. Its ability to selectively target and destroy cancer cells while stimulating antitumor immunity holds tremendous potential for improved therapeutic outcomes. Ongoing research and clinical trials continue to shed light on the safety and efficacy of NDV-based therapies. If successful, this viral knock on cancer's door may hold the key to unlocking a brighter and more effective future in cancer treatment, providing hope to patients and oncologists alike. Oncolytic virotherapy harnesses the selective replication of viruses in cancer cells while sparing healthy tissues, leading to tumor lysis and immune system activation. The concept dates back to the early 20th century, but it gained significant attention in the 1990s with the advent of genetic engineering techniques that allowed for the manipulation and modification of viruses. Among the various oncolytic viruses being explored, the Newcastle Disease Virus stands out as a promising candidate due to its unique properties [2].

Literature Review

The Newcastle Disease Virus, also known as Avian Paramyxovirus Type 1, belongs to the family Paramyxoviridae. It primarily affects birds, causing severe respiratory and neurological symptoms, and is highly contagious among avian populations. In humans, NDV typically causes mild flu-like symptoms, making it a favorable candidate for virotherapy due to its apparent safety profile. The oncolytic activity of NDV arises from its inherent ability to selectively target and replicate within cancer cells. NDV uses a two-pronged approach to induce cancer cell death. Firstly, the virus exploits the deficient antiviral response in cancer cells, allowing it to replicate unchecked. Secondly, NDV inducestumor cell apoptosis and lysis by activating host immune responses. This dual mechanism of action makes NDV an attractive agent for cancer therapy.

Beyond its direct cytolytic effects, NDV has demonstrated potent immunomodulatory properties. Oncolytic viruses like NDV can initiate an immunogenic cell death process, releasing tumor antigens and danger signals. This process stimulates the host immune system, promoting the activation of cytotoxic T cells and natural killer cells. Moreover, NDV enhances the production of pro-inflammatory cytokines, further aiding in the destruction of cancer cells and promoting antitumor immune responses. Several preclinical studies have provided encouraging results for NDV-based virotherapy [3]. In animal models, NDV has exhibited significant antitumor activity against a variety of cancers, including breast, prostate, lung, and pancreatic cancer. These studies have demonstrated tumor regression, increased survival rates, and a reduction in metastatic spread following NDV treatment.

Discussion

In clinical trials, NDV has been tested in various cancer types, either alone or in combination with conventional treatments. While early-phase trials have primarily focused on safety and feasibility, there have been promising signs of efficacy. Some patients showed disease stabilization or partial responses, especially in advanced stages of cancer where conventional treatments had limited success. Despite its potential, oncolytic virotherapy using NDV faces several challenges. One of the significant hurdles is the host immune response against the virus itself. Neutralizing antibodies can limit the efficacy of repeat administrations, which may be required for long-term therapeutic benefits. Additionally, the safety of NDV administration in patients with compromised immune systems needs careful consideration [4].

Once inside the tumor cell, NDV undergoes replication, leading to the synthesis of viral progeny. This replication process results in the lysis of the host cell, causing the release of viral particles and amplifying the viral spread throughout the tumor microenvironment. Importantly, NDV's replication selectively occurs in tumor cells, leaving normal cells unharmed. NDV also stimulates the activation of the immune system, making it a potential inducer of antitumor immunity. As infected cancer cells undergo apoptosis, they release tumor antigens, effectively presenting them to the immune system. This provokes an immune response, promoting the activation of cytotoxic T cells and Natural Killer (NK) cells. Additionally, NDV-infected cancer cells upregulate pro-inflammatory cytokines, further enhancing the immune response against the tumor [5].

The encouraging preclinical data on NDV's oncolytic properties have prompted the initiation of several clinical trials to evaluate its safety and efficacy in cancer patients. As of the current date, clinical trials investigating NDV-based therapies have primarily focused on advanced or refractory solid tumors. Early-phase clinical trials have demonstrated the safety of NDV administration with manageable adverse effects. Encouragingly, some studies have reported promising signs of antitumor activity and disease stabilization in patients with advanced cancers who had exhausted standard treatment options [6].

Conclusion

Another limitation is the need to develop better targeted delivery systems for NDV. While NDV exhibits tumor selectivity to some extent, improving its specificity for cancer cells could reduce potential side effects and enhance therapeutic efficacy. The progress of oncolytic virotherapy with NDV holds great promise for the future of cancer treatment. Advancements in genetic engineering techniques could allow for the creation of modified NDV strains with enhanced tumor specificity and reduced immunogenicity. Combination therapies, involving NDV and other immunotherapeutic agents, could also offer synergistic effects, further bolstering the immune response against cancer. The development of personalized medicine approaches could help identify patients most likely to benefit from NDV virotherapy. Biomarkers predictive of treatment response may aid in patient selection, ensuring that the therapy is administered to those who will derive the most significant benefit.

Acknowledgement

Conflict of Interest

Conflict of Interest

There is no conflict of interest by author.

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