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Review
. 2023 Jun 12:14:1188526.
doi: 10.3389/fmicb.2023.1188526. eCollection 2023.

Development and application of oncolytic viruses as the nemesis of tumor cells

Xiao Zhu  1   2   3 , Chenyang Fan  4 , Zhuolong Xiong  2 , Mingwei Chen  2 , Zesong Li  5 , Tao Tao  6 , Xiuqing Liu  7
Affiliations
Review

Development and application of oncolytic viruses as the nemesis of tumor cells

Xiao Zhu et al. Front Microbiol. .

Abstract

Viruses and tumors are two pathologies that negatively impact human health, but what occurs when a virus encounters a tumor? A global consensus among cancer patients suggests that surgical resection, chemotherapy, radiotherapy, and other methods are the primary means to combat cancer. However, with the innovation and development of biomedical technology, tumor biotherapy (immunotherapy, molecular targeted therapy, gene therapy, oncolytic virus therapy, etc.) has emerged as an alternative treatment for malignant tumors. Oncolytic viruses possess numerous anti-tumor properties, such as directly lysing tumor cells, activating anti-tumor immune responses, and improving the tumor microenvironment. Compared to traditional immunotherapy, oncolytic virus therapy offers advantages including high killing efficiency, precise targeting, and minimal side effects. Although oncolytic virus (OV) therapy was introduced as a novel approach to tumor treatment in the 19th century, its efficacy was suboptimal, limiting its widespread application. However, since the U.S. Food and Drug Administration (FDA) approved the first OV therapy drug, T-VEC, in 2015, interest in OV has grown significantly. In recent years, oncolytic virus therapy has shown increasingly promising application prospects and has become a major research focus in the field of cancer treatment. This article reviews the development, classification, and research progress of oncolytic viruses, as well as their mechanisms of action, therapeutic methods, and routes of administration.

Keywords: PD-1; adenovirus; anti-tumor immune response; herpes simplex virus; oncolytic virus; tumor cells.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The pie chart shows the study stage of 147 clinical studies, most of which were in Phase I (n = 72, 48.9%), Phase I/II (n = 34, 23.1%), and Phase II (N = 36, 24.5%) and Phase III (n = 5, 3.40%).
Figure 2
Figure 2
Analysis of administration pattern and indications in clinical study registry. (A) Intratumoral injection (n = 73) and intravenous injections (n = 43) were the main administrative methods in the study, and the number of other administrative methods is shown in the figure. (B) Shows the number of studies on tumors where intratumoral injection can be used, among which melanoma has the largest number of studies (n = 17, 20.5%), which are mostly used in benign solid tumors but also some malignant tumors. (C) Shows the number of studies of tumors that can be injected intravenously, the majority of which are malignant solid tumors. (D) Showing tumors that can be treated by administration other than intratumoral and intravenous injections, it can be seen that glioblastoma is a tumor that can be treated by virtually every administration method.
Figure 3
Figure 3
Analysis of combination therapy in the registry of clinical studies. (A) Combination therapy in the study was mainly immune checkpoint inhibitors and chemotherapy, and the other combination therapy methods were also studied in A certain number of studies. (B) This shows the number of studies on tumors that can be treated with combination therapy, with melanoma being the largest. And breast cancer and glioblastoma also have a large number of studies, including the majority of solid tumors. (C) Showed the number of studies on tumors treated with immune checkpoint inhibitors combined with OVs, with melanoma being the largest, accounting for 25.6%. (D) This shows the number of studies on tumors treated by chemotherapy combined with OVs, with the largest number being abdominal tumors, followed by brain tumors.
Figure 4
Figure 4
Oncolytic virus (OV) after entering the host can identify receptors on cells, meet with receptors unique to cancer cells can enter the cancer cells, and can breed will kill cancer cells in cancer cells, and cancer cells burst into offspring OVs are released, and can infect nearby cancer cells and kill, and in the normal cells of the human body does not have this kind of peculiar receptor, OVs cannot get into normal cells to multiply.
Figure 5
Figure 5
Oncolytic viruses can change the microenvironment of tumor cells from “cold” to “hot.” (A) OVS can specifically attack the supply vessels of tumor cells, making tumor cells have no nutritional supply to kill tumor cells, while OVS have no response to the supply vessels of normal cells. (B) After OVs act on tumor cells, tumor cells can release a large number of signal molecules to activate non-specific immune cells outside tumor cells. A large number of activated immune cells infiltrate tumor cells and accelerate the process of killing tumor cells. (C) Cleaved tumor cells will release a large amount of tumor protein, but non-specific immune cells can use this tumor protein to continuously play an immune role and form a long-term anti-tumor effect. (D) OV activates specific antigens in tumor cells, which can be expressed by antigen-presenting cells and induce the killing effect of T cells.
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