Broad Application Prospects of Oncolytic Virus in Future Immunocombination Therapy

Tumor immunotherapy has made a series of advances in recent years which has changed the treatment pattern of many cancers. At the same time, however, tumor immunotherapy has also exposed bottlenecks such as insufficient population, which limits its application. In order to make it more potential, researchers are looking for cooperators to form more effective combination therapies. In many potentials, oncolytic virus is one of the most interesting new treatments. Recently, a review of the broad application prospects of oncolytic viruses in future immunocombination therapy being published on Nature Reviews | Cancer.

Oncolytic viruses refer to a class of viruses that effectively infect and destroy cancer cells. Due to the nature of the virus, this therapy can be administered either systemically or topically to treat primary and metastatic tumors. When cancer cells rupture and die under the infection of a virus, newly generated virus particles are released, then further infecting surrounding cancer cells. From the mechanism point of view, it can not only directly kill the tumor, but also stimulate the body's immune response and enhance the anti-tumor effect.

In order to make the oncolytic virus to effectively target cancer cells, specific targeting of tumors is a major focus in research and development. Interestingly, tumors are naturally suitable for attack by oncolytic viruses. When genes such as RAS, TP53, RB1, and PTEN are mutated, the anti-viral infection ability of cancer cells will be weakened and offering the oncolytic virus a chance. In response to these weaknesses in cancer cells, researchers have developed a variety of viruses that can effectively target tumors.

T cells must undergo four critical steps in order to trigger a successful anti-tumor response. The oncolytic virus can assist T cells in the following four steps:

. T cell priming

The initiation of the T cell response is inseparable from the recognition of specific epitopes, and this complex process is inseparable from the work of antigen presenting cells. In cancer, the process of antigen presentation is often negatively affected, leaving the tumor "cold" immunologically. The oncolytic virus can achieve a similar effect as a "vaccine", promoting the presentation and recognition of tumor-associated antigens.

Local oncolytic virus therapy can cleave cancer cells, release a large number of tumor-associated antigens, and create an immunogenic cytokine environment that facilitates antigen-presenting cells to perform their functions. This idea has been verified in many experiments. Some researchers have found that the mosaic of poliovirus and rhabdovirus can lead to the release of tumor antigens and the development of a class I interferon response. These stimuli eventually induce tumor-specific T cell population proliferation.

The researchers point out that the advantage of this method is that it does not need prior knowledge of tumor-associated antigens which makes it a simple and individualized vaccine development tool. However, this method can not necessarily induce sufficient T cell responses, researchers believe that the addition of tumor-associated viral vectors to oncolytic viruses may improve outcomes.

. Trafficking and Infiltration

T cells in the circulation can move to the tumor site for infiltration, which plays a decisive role in the prognosis of patients. The use of oncolytic viruses is expected to enhance the infiltration of T cells into tumors.

First, viral infections can stimulate potential class I interferon responses, stimulate the production of chemokines, and recruit T cells. Second, oncolytic viruses can induce TNF, IL-1?, and complement responses, upregulate the expression of selectin on endothelial cells, and provide a key signal for T cell infiltration. Third, the oncolytic virus is expected to target specific cancer-causing signaling pathways through transformation. Fourth, oncolytic viruses can encode T cell chemotactic agents, and it is expected that T cells will be directly recruited without fear of chemokine expression defects in the tumor environment. The researchers also pointed out that the tumor virus can also help overcome structural obstacles and further help T cell infiltration. For example, it can attract neutrophils to release inflammatory mediators in the tumor microenvironment and proteases with cytotoxic and extracellular matrix (ECM) degradation properties.

. Circumventing Immune Suppression

Even if T cells successfully infiltrate in the oncolytic, it still does not mean that they can effectively attack the tumor. The researchers point out that T cells still need to overcome the immunosuppressive molecules in the environment after entering the tumor. Subsequent findings indicate that the use of oncolytic viruses allows T cells to respond to tumor antigens and prevent tumor recurrence. Moreover, the use of immunological checkpoint inhibitors can further enhance the therapeutic effect. Other preclinical trials have also demonstrated the potential of combination of oncolytic viruses with immunological checkpoint inhibitors.

. Engagement of tumour cells

The final step in successful immunotherapy is the recognition, binding, and attack of tumor cells by T cells. In order to avoid the recognition of T cells, tumor cells can down-regulate the pathways involved in antigen presentation and MHC class I. The oncolytic virus is expected to reverse to some extent. The researchers also pointed out that the oncolytic virus is expected to use a new method to promote the binding of T cells to tumor cells.

The future of oncolytic virus therapy

There are two potential development directions of the oncolytic virus at this stage: One is to combine with T cell therapy to assist T cells in the proliferation, movement and efficacy of local tumor microenvironment. The second is that researchers are expected to develop a better oncolytic virus and further expand its potential through further understanding of the immune mechanism through further understanding of the immune mechanism.

There is no doubt that the future of oncolytic viruses is full of opportunities. We should combine this potential tool with existing therapies, and apply the former's ability to influence the immune response to effectively remove residual tumor lesions. With the continuous clarification of the anti-tumor mechanism of the immune system, oncolytic virus is expected to provide an important platform for immunotherapy.

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