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Review
. 2024 Mar 13:15:1272351.
doi: 10.3389/fimmu.2024.1272351. eCollection 2024.

Recent progress in combination therapy of oncolytic vaccinia virus

Seyedeh Nasim Mirbahari  1   2 , Miles Da Silva  3   4 , Abril Ixchel Muñoz Zúñiga  5   6 , Nika Kooshki Zamani  5   6 , Gabriel St-Laurent  5   6 , Mehdi Totonchi  2 , Taha Azad  5   6
Affiliations
Review

Recent progress in combination therapy of oncolytic vaccinia virus

Seyedeh Nasim Mirbahari et al. Front Immunol. .

Abstract

In recent years, oncolytic viruses have emerged as promising agents for treating various cancers. An oncolytic virus is a non-pathogenic virus that, due to genetic manipulation, tends to replicate in and cause lysis of cancerous cells while leaving healthy cells unaffected. Among these viruses, vaccinia virus is an attractive platform for use as an oncolytic platform due to its 190 Kb genome with a high capacity for encoding therapeutic payloads. Combining oncolytic VV therapy with other conventional cancer treatments has been shown to be synergistic and more effective than monotherapies. Additionally, OVV can be used as a vector to deliver therapeutic payloads, alone or in combination with other treatments, to increase overall efficacy. Here, we present a comprehensive analysis of preclinical and clinical studies that have evaluated the efficacy of oncolytic vaccinia viruses in cancer immunotherapy. We discuss the outcomes of these studies, including tumor regression rates, overall survival benefits, and long-term responses. Moreover, we provide insights into the challenges and limitations associated with oncolytic vaccinia virus- based therapies, including immune evasion mechanisms, potential toxicities, and the development of resistance.

Keywords: cancer therapy; combination therapy; immunotherapy; oncolytic vaccinia virus; oncolytic virus.

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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
Targeting cancer cells by different treatment methods. 1. OVVs increase the expression of interferon by entering cancer cells. 2. Radiotherapy causes damage to the DNA of the tumor cell, while it does not damage the DNA of the vaccinia virus due to the difference in the time of injection. 3. Interferon therapy recruit immune cells. 4. PDL-1 protein injection or gene insertion increases the response to immunotherapy methods. 5. Chemotherapy destroys cancer cells by causing inflammation. 6. Blockage of immunochecking inhibitors such as anti-PD-1 causes the recognition of receptors by T-cells. 7 and 8 T-cells and CAR-T cells also destroy cancer cells by binding receptors.
Figure 2
Figure 2
T-cells are inhibited when immune-checkpoints bind to ligands on tumor cells and APCs. PD-L1/L2, CD40, CD80/86, are expressed on tumor cells or APCs. Their expression is induced and maintained by many factors. PD-1, CTLA-4, CD40L and CD28 are expressed on exhausted effector T-cells. CTLA-4, which interacts with its ligands B7-1/CD80 and B7-2/CD86, or PD-1, binding to its ligand PD-L1, generate inhibitory signals, dampening T-cell immune responses. These receptors, CTLA-4 and PD-1, serve as targets for ICIs like anti-CTLA-4, PD-1, and PD-L1 aiming to decrease immune cell inhibition.
Figure 3
Figure 3
Different types of ICIs applications. (A) OVV injection alone increases the ICIs expression which is due to the increase of interferon γ levels through the JAK/STAT pathway. (B) Insertion of PD-1 or PD-L1 in OVV induce the overexpression of ICIs which increase the success rate of immunotherapy. (C) Insertion of anti-PD-1 or anti-PD-L1 antibody, block the interaction of ICIs with T-cells, therefore t-cell can inhibit the tumor cells. (D) Injection of OVV and anti-PD-1 antibody or anti-PD-L1 antibody in a designed regimen not only recruit immune cells, but also inhibit the interaction of ICIs with T-cells.
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by the grant the Canadian Cancer Society.

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