Benefits and Drawbacks for Therapeutic Programming of Tumor Microenvironment

Hesse Grass^*
*Correspondence: Hesse Grass, Department of Clinical Virology, Heidelberg University, Baden-wurttemberg, Germany, Email:

Introduction

Viral vectors have emerged as a promising strategy for treating cancer by selectively replicating lytic viruses inside tumors. There are two main types of mechanisms that underlie viruses ability to fight cancer. One is the particular obliteration of growth cells by oncolytic infection replication. The antiviral response of the host cell and the expression of virus cell surface receptors both have an impact on this effect. The induction of systemic anti-tumor immunity is linked to the other mechanism of virus-mediated antitumor activity. It is becoming increasingly apparent that innate and adaptive immunity against cancer cells can be effectively induced through the use of antiviral immune responses.

Description

The tumor microenvironment is manipulated by tumors to prime the local immune response, suppressing both innate and acquired immunity. Changes in the tumour microenvironment (TME) may be common in many types of tumors, suggesting the possibility of therapeutic interventions into tumorsupporting mechanisms to treat various types of cancers despite the genetic instability of cancer cells and the existence of multiple mechanisms to evade the immune response. The availability of tumor epitopes for T cell activation is greatly enhanced by tumor antigens released by viral infection. The discovery of tumor-specific neo antigens that have no self-tolerance and the approval of effective immune checkpoint inhibitors (CPIs) have facilitated the clinical development of novel vector-based cancer therapies. Using CPIs to reactivate the patient's immune system to fight their own cancer is producing encouraging results. CPIs therapy, on the other hand, currently benefits only a small number of patients. The T cells' inability to infiltrate and recognize the tumor is one factor. The virus vector could localize the expression of immunomodulatory genes, thereby avoiding issues with systemic toxicity while simultaneously stimulating antitumor immunity [1-5].

The development of effective cancer vaccines turned out to be more challenging, primarily due to the immune-suppressive microenvironment created by cancer cells, the low immunogenicity of autologous tumourassociated antigens (TAAs), and the plasticity of cancer cells. While the use of vaccines to prevent infectious diseases is a story of great success, the development of effective cancer vaccines turned out to be more challenging. Only a few therapeutic cancer vaccines were approved by the FDA in 2010 to treat asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. These vaccines only occasionally produced clinical benefits. Attenuated versions of common human pathogens are present in many of the oncolytic viruses that are currently being tested in clinical trials. They have been hereditarily designed to additionally decrease their pathogenicity and to increment oncolytic strength and particularity for malignant growth tissue. Treatments for cancer and vaccines based on RNA and DNA viral vectors are all subjects of clinical trials. A virus with a genome made of doublestranded DNA is the best candidate for such manipulations because it has a more stable genome and is less likely to undergo dangerous mutations.

The therapy target is the primary consideration when selecting the virus vector. Host cells or cancer cells could be among these. Latent virus infection without cell death is required for the purpose of reprogramming immune cells. The tissue or tumor of interest ought to be able to be targeted by the vector. In a perfect world, each specific cancer must be assessed for the remedial infection contamination/replication productivity, as training demonstrates the way that the growth cell powerlessness to the infection vector could be somewhat individual and challenging to foresee. Since this is the most important factor in determining the efficacy of virus therapy, it would appear that a reliable test protocol for individualized tumor infectivity evaluation for the main virus vectors used in clinics needs to be developed. The possibility of pre-existing immunity against the vector, which may have a significant impact on the outcome of therapy, is a second crucial factor that needs to be evaluated. Although the majority of large vectors are intended for local administration, it should be possible to distribute them systemically. In most cases, there must be some compromise made between the safety of the treatment and its efficacy. Intravenous infusion gives a possible open door to the infection to taint all disease cells, including distal metastases. However, the immune system of the host may be able to neutralize viral particles that are injected throughout the body before they reach the intended cells. Although the dense extracellular matrix of the tumor restricts the spread of virus particles outside the injection area, the intratumoral injection can ensure that virus particles reach the tumor directly. Consequently, whether systemic or local administration is used, the use of replication-deficient virus vectors is safe but less effective than using attenuated replication-competent virus types in terms of therapy efficacy.

Conclusion

The comprehension of general immunosuppressive TME characteristics, the discovery of CPIs, and advancements in tumour selective virus vector engineering with a variety of vector options present excellent opportunities for the continued successful application of virotherapy in the treatment of cancer. It is important to carefully examine individual differences in immune cell composition and response to tumor immunotherapy during treatment. Depending on whether the tumor is inflamed or poorly immunogenic, various treatment strategies should be developed and implemented. Prior to beginning treatment, it would be of the utmost importance to determine the individual sensitivity of the tumor or virus vector and to evaluate the TME status. Antibody levels should be checked both before and during treatment for viruses, such as adenoviruses and MV, for which there is a high likelihood that immunity already exists. Based on (i) tumour sensitivity to the chosen virus vectors, (ii) TME composition evaluation, and (iii) monitoring virus vector replication and cytokine release during patient treatment, future directions should cover the rules for selecting a personalised virus treatment approach. Viral vectors have a lot of potential for effective, safe, and nontoxic cancer immunotherapy and would undoubtedly become a common treatment tool.

Acknowledgement

None.

Conflict of Interest

The authors declare that there is no conflict of interest associated with this manuscript

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