Genetic Modifications That Expand Oncolytic Virus Potency

doi:10.3389/fmolb.2022.831091

Review

. 2022 Jan 26:9:831091.

doi: 10.3389/fmolb.2022.831091. eCollection 2022.

Genetic Modifications That Expand Oncolytic Virus Potency

Francisca Cristi¹, Tomás Gutiérrez², Mary M Hitt³, Maya Shmulevitz¹

Affiliations

¹ Shmulevitz Laboratory, Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
² Goping Laboratory, Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
³ Hitt Laboratory, Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

PMID: 35155581
PMCID: PMC8826539
DOI: 10.3389/fmolb.2022.831091

Review

Genetic Modifications That Expand Oncolytic Virus Potency

Francisca Cristi et al. Front Mol Biosci. 2022.

. 2022 Jan 26:9:831091.

doi: 10.3389/fmolb.2022.831091. eCollection 2022.

Authors

Francisca Cristi¹, Tomás Gutiérrez², Mary M Hitt³, Maya Shmulevitz¹

Affiliations

¹ Shmulevitz Laboratory, Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
² Goping Laboratory, Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
³ Hitt Laboratory, Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

PMID: 35155581
PMCID: PMC8826539
DOI: 10.3389/fmolb.2022.831091

Abstract

Oncolytic viruses (OVs) are a promising type of cancer therapy since they selectively replicate in tumor cells without damaging healthy cells. Many oncolytic viruses have progressed to human clinical trials, however, their performance as monotherapy has not been as successful as expected. Importantly, recent literature suggests that the oncolytic potential of these viruses can be further increased by genetically modifying the viruses. In this review, we describe genetic modifications to OVs that improve their ability to kill tumor cells directly, to dismantle the tumor microenvironment, or to alter tumor cell signaling and enhance anti-tumor immunity. These advances are particularly important to increase virus spread and reduce metastasis, as demonstrated in animal models. Since metastasis is the principal cause of mortality in cancer patients, having OVs designed to target metastases could transform cancer therapy. The genetic alterations reported to date are only the beginning of all possible improvements to OVs. Modifications described here could be combined together, targeting multiple processes, or with other non-viral therapies with potential to provide a strong and lasting anti-tumor response in cancer patients.

Keywords: cancer therapy; genetic modifications; metastasis; oncolytic potency; 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**
Mechanisms of genetic modifications to improve oncolytic viruses (OVs) dissemination to distant metastases. OVs have been modified to expand their oncolytic potency and with that to spread more efficiently to metastatic sites. These modifications were categorized in 4 mechanisms: enhancing virus replication and killing ability (top left, section A and Table 1); dismantling the tumor microenvironment (bottom right, section B and Table 2); inhibiting angiogenesis (top right, section C and Table 3); and altering tumor signaling (bottom left, section D and Table 3).

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References

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[1] Andtbacka R. H. I., Kaufman H. L., Collichio F., Amatruda T., Senzer N., Chesney J., et al. (2015). Talimogene Laherparepvec Improves Durable Response Rate in Patients with Advanced Melanoma. Jco 33 (25), 2780–2788. 10.1200/jco.2014.58.3377 - DOI - PubMed

[2] Andtbacka R. H. I., Kaufman H. L., Collichio F., Amatruda T., Senzer N., Chesney J., et al. (2015). Talimogene Laherparepvec Improves Durable Response Rate in Patients with Advanced Melanoma. Jco 33 (25), 2780–2788. 10.1200/jco.2014.58.3377 - DOI - PubMed

[3] Annels N. E., Mansfield D., Arif M., Ballesteros-Merino C., Simpson G. R., Denyer M., et al. (2019). Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent against Non Muscle-Invasive Bladder Cancer. Clin. Cancer Res. 25 (19), 5818–5831. 10.1158/1078-0432.ccr-18-4022 - DOI - PubMed

[4] Annels N. E., Mansfield D., Arif M., Ballesteros-Merino C., Simpson G. R., Denyer M., et al. (2019). Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent against Non Muscle-Invasive Bladder Cancer. Clin. Cancer Res. 25 (19), 5818–5831. 10.1158/1078-0432.ccr-18-4022 - DOI - PubMed

[5] Annes J. P., Munger J. S., Rifkin D. B. (2003). Making Sense of Latent TGFbeta Activation. J. Cel Sci 116 (Pt 2), 217–224. 10.1242/jcs.00229 - DOI - PubMed

[6] Annes J. P., Munger J. S., Rifkin D. B. (2003). Making Sense of Latent TGFbeta Activation. J. Cel Sci 116 (Pt 2), 217–224. 10.1242/jcs.00229 - DOI - PubMed

[7] Atzeni F., Sarzi-Puttini P. (2013). Tumor Necrosis Factor. Brenner's Encyclopedia of Genetics2013, 229–231.

[8] Atzeni F., Sarzi-Puttini P. (2013). Tumor Necrosis Factor. Brenner's Encyclopedia of Genetics2013, 229–231.

[9] Baghban R., Roshangar L., Jahanban-Esfahlan R., Seidi K., Ebrahimi-Kalan A., Jaymand M., et al. (2020). Tumor Microenvironment Complexity and Therapeutic Implications at a Glance. Cell Commun Signal 18 (1), 59. 10.1186/s12964-020-0530-4 - DOI - PMC - PubMed

[10] Baghban R., Roshangar L., Jahanban-Esfahlan R., Seidi K., Ebrahimi-Kalan A., Jaymand M., et al. (2020). Tumor Microenvironment Complexity and Therapeutic Implications at a Glance. Cell Commun Signal 18 (1), 59. 10.1186/s12964-020-0530-4 - DOI - PMC - PubMed

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Genetic Modifications That Expand Oncolytic Virus Potency

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Genetic Modifications That Expand Oncolytic Virus Potency

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Conflict of interest statement

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