Oncolytic Virotherapy – “A Viral Assault on Tumors”

1. Introduction

Oncolytic virotherapy is a type of cancer treatment that uses viruses to target and kill cancer cells. Although it has been mainly researched and developed for human medicine, there is growing interest in applying this therapy to livestock as well. Oncolytic viruses, a category encompassing both naturally occurring and laboratory-modified viruses, possess a unique capability to infect and eliminate tumor cells while sparing healthy ones. This selectivity is achieved through genetic engineering or inherent traits that enable these viruses to replicate effectively within cancer cells. The field of virotherapy has evolved significantly, offering a diverse array of viruses with enhanced attributes, including improved systemic delivery, heightened tumor specificity, and superior oncolytic potency. Beyond their traditional role of directly eradicating cancer cells, emerging research suggests that certain oncolytic viruses may, in part, operate by eliciting an immune response against cancer.

When an oncolytic virus invades a tumor cell, it multiplies until the cell ruptures, releasing tumor antigens and triggering recognition by the immune system. This dual mechanism of cell lysis and immune response has been termed the “vaccine effect”.Talimogenelaherparepvec (Imlygic® or T-VEC), an armed oncolytic virus engineered to stimulate immune cell production, gained FDA approval for melanoma treatment. This therapy involves localized injections into tumors, reducing the risk of herpes transmission.

2. The characteristics of oncolytic viruses can be summarized as follows:

2.1. Oncolytic Properties: These viruses selectively replicate within malignant cells, causing tumor cell lysis. Normal cells remain unaffected due to viral clearance. The release of viral progeny further infects neighboring tumor cells.

2.2. Immuno-Stimulatory Properties: Viral replication leads to oncolysis, releasing tumor-specific antigens and pattern molecules, initiating the presentation of antigens by dendritic cells and the activation of tumor-specific T cells. Concurrently, viral infection induces inflammation and chemokine release, attracting T cells to the tumor.

2.3.Oncolytic Viruses as Transgene Delivery Platform: Some oncolytic viruses can be modified to carry transgenes, such as cytokines or antibodies, for targeted delivery to the tumor microenvironment, amplifying the antitumor immune response. These are referred to as “armed oncolytic viruses”.

3. Mode of action of Oncolytic Viruses:

3.1.Oncolytic viruses (OVs) are specifically designed to replicate within cancer cells, leading to the destruction of cancerous tissue without causing harm to healthy cells. This unique mechanism of action holds the potential to induce cancer regression or even complete cure in patients who have not responded to current treatment methods.Various viruses, such as adenovirus, herpes simplex virus, reovirus, poliovirus, and Newcastle disease virus, have demonstrated strong oncolytic properties.

3.2. Many OVs not only directly destroy cancer cells but also stimulate the body’s immune response against cancer by releasing tumor-specific antigens upon cell lysis. This immune response, often referred to as the “vaccine effect,” is further enhanced by the local inflammation caused by the replication of oncolytic viruses, which also aids in the destruction of the tumor’s supporting structures, including its vasculature.

3.3. Due to this multifaceted approach, encompassing cell lysis, systemic anti-cancer immune response, and local inflammation, OVs show immense promise as novel anticancer agents. Additionally, combining OV therapy with conventional cancer treatments like chemotherapy and immunotherapy is feasible, further expanding their potential effectiveness.

4. Tactics for addressing obstacles in viral oncotherapy:

4.1. Resisting Antibody Neutralization: Employing genetic and chemical methods to shield the virus from antibody neutralization.

4.2. Improving Tumor Specificity: Targeting tumor-associated receptors and controlling post-entry viral replication to enhance specificity.

4.3. Enhancing Therapeutic Synergy: Developing rational combinations of virus families, engineering strategies, and complementary therapies to optimize efficacy, especially in cases with unmet clinical needs.

5. Obstacles and difficulties encountered in the field of oncolytic virotherapy include:

5.1. Virus Selection: Identifying suitable oncolytic viruses for specific livestock species is critical, necessitating tailored approaches.

5.2. Safety Concerns: Robust safety assessments and regulatory frameworks are essential to prevent unintended consequences when introducing oncolytic viruses to livestock populations.While oncolytic virotherapy offers potential benefits, it also presents adverse effects, including fever and flu-like symptoms. Additionally, there is a need to address concerns about virus shedding in bodily fluids. Advancements in virus production techniques may allow more aggressive dosing in future trials, emphasizing the importance of tumor specificity for maintaining safety profiles.

5.3. Treatment Delivery: Developing effective delivery methods, such as direct injection or aerosol delivery, is crucial for livestock applications.

5.4. Economic Feasibility: The cost-effectiveness of oncolytic virotherapy in livestock must be evaluated, considering production, storage, distribution, and market demand.

6. Conclusion:

Oncolytic virotherapy holds the promise of transforming cancer treatment for livestock. Through continued research and a thorough examination of its challenges and prospects, this pioneering approach may open novel pathways for combating cancer and enhancing the health and welfare of animal populations. Nonetheless, realizing the potential of oncolytic virotherapy in treating livestock cancer demands comprehensive research efforts to tackle obstacles and evaluate safety, effectiveness, and economic feasibility within this specific context.

Figure.1 Mode of action of oncolytic viruses