Oncolytic Viruses: A Key Step toward Cancer Immunotherapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Immunology and Immunotherapy".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 7545

Special Issue Editor


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Guest Editor
Centre for Cancer Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK
Interests: immunotherapy; tumor; oncolytic virus

Special Issue Information

Dear Colleagues,

The link between cancer regression and viral infection has been noted for over a century. In 1904, Dock reported the spontaneous regression of leukemia in a patient co-incidentally infected with influenza in the American Journal of Medical Sciences. With the much more recent emergence of genetic editing techniques and improved understanding of both virus biology and tumorigenesis, we are now able to build on this observation to create safe and efficacious cancer treatments in the form of oncolytic viruses (OVs). OVs are a potential powerhouse in our fight against tumors. More so than many other current treatment options, they can attack cancers in multiple ways to eliminate the tumor and its microenvironment and prevent recurrence. In their simplest form, oncolytic viruses are able to selectively replicate in and kill cancer cells. At the site of infection and cell death, immune responses against tumor antigens are triggered. These remodel the tumor microenvironment into a less tumor-supportive milieu and trigger adaptive immunity that results in regression and long-term control over tumor growth. More current ‘arming’ strategies have demonstrated significant improvement in the induction of anti-tumor immune responses.

Despite their pre-clinical efficacy and the clinical application of oncolytic herpes simplex virus in melanoma patients, few oncolytic viruses have emerged as demonstrating significant clinical efficacy. 

In this Special Issue of Cancers, we aim to collate reviews detailing the most up-to-date clinical information regarding the application of oncolytic viruses and summarize the responses to the challenges these trials are revealing. We also aim to highlight future directions for the field, including more potent combinations and arming strategies, in order to realize the full potential of these agents.

Dr. Louisa Chard Dunmall
Guest Editor

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Keywords

  • oncolytic viruses
  • tumor microenvironment
  • immunotherapy
  • checkpoint inhibitors
  • BiTE
  • stroma
  • CAR-T

Published Papers (5 papers)

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Research

15 pages, 2347 KiB  
Article
Intratumoral Delivery of Interleukin 9 via Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in Tumor Models
by Junjie Ye, Lingjuan Chen, Julia Waltermire, Jinshun Zhao, Jinghua Ren, Zongsheng Guo, David L. Bartlett and Zuqiang Liu
Cancers 2024, 16(5), 1021; https://doi.org/10.3390/cancers16051021 - 29 Feb 2024
Viewed by 1202
Abstract
The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in [...] Read more.
The success of cancer immunotherapy is largely associated with immunologically hot tumors. Approaches that promote the infiltration of immune cells into tumor beds are urgently needed to transform cold tumors into hot tumors. Oncolytic viruses can transform the tumor microenvironment (TME), resulting in immunologically hot tumors. Cytokines are good candidates for arming oncolytic viruses to enhance their function in this transformation. Here, we used the oncolytic vaccinia virus (oVV) to deliver interleukin-9 (IL-9) into the tumor bed and explored its antitumor effects in colon and lung tumor models. Our data show that IL-9 prolongs viral persistence, which is probably mediated by the up-regulation of IL-10. The vvDD-IL-9 treatment elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, granzyme B, and perforin. IL-9 expression increased the percentages of CD4+ and CD8+ T cells in the TME and decreased the percentage of oVV-induced immune suppressive myeloid-derived suppressor cells (MDSC), leading to potent antitumor effects compared with parental virus treatment. The vvDD-IL-9 treatment also increased the percentage of regulatory T cells (Tregs) in the TME and elevated the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4, but not GITR. The combination therapy of vvDD-IL-9 and the anti-CTLA-4 antibody, but not the anti-GITR antibody, induced systemic tumor-specific antitumor immunity and significantly extended the overall survival of mice, indicating a potential translation of the IL-9-expressing oncolytic virus into a clinical trial to enhance the antitumor effects elicited by an immune checkpoint blockade for cancer immunotherapy. Full article
(This article belongs to the Special Issue Oncolytic Viruses: A Key Step toward Cancer Immunotherapy)
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14 pages, 3094 KiB  
Article
A New HEK293 Cell with CR2 Region of E1A Gene Deletion Prevents the Emergence of Replication-Competent Adenovirus
by Xueqi Lian, Xiaoyan Zhao, Jingjing Zhong, Chenglin Zhang, Yongchao Chu, Yaohe Wang, Shuangshuang Lu and Zhimin Wang
Cancers 2023, 15(24), 5713; https://doi.org/10.3390/cancers15245713 - 5 Dec 2023
Viewed by 1214
Abstract
Purpose: To eliminate the contaminants of Replication-Competent Adenovirus (RCA) during high titer recombinant oncolytic adenovirus production. Methods: At first, we detected E1A copy numbers of different sources of 293 cells using Q-PCR, and we screened a subclone JH293-C21 of the JH293 cell line [...] Read more.
Purpose: To eliminate the contaminants of Replication-Competent Adenovirus (RCA) during high titer recombinant oncolytic adenovirus production. Methods: At first, we detected E1A copy numbers of different sources of 293 cells using Q-PCR, and we screened a subclone JH293-C21 of the JH293 cell line (purchased from ATCC) with lower early region 1A (E1A) copy numbers and higher adenovirus production ability. Then, we deleted the conserved region (CR)2 of the E1A gene in this subclone using the CRISPR-Cas9 system and obtained a stable cell clone JH293-C21-C14 with lower E1A expression, but the RCA formation had no significant reduction. Then, we further deleted the CR2 of JH293-C21-C14 cells with the CRISPR-Cas9 system and obtained a strain of cells named JH293-C21-C14-C28. Finally, we detected the capacity for cell proliferation, adenovirus production, and RCA formation in the production of recombinant adenovirus. Results: The JH293-C21-C14-C28 cells had a similar cell proliferation ability and human adenovirus production as JH293-C21 cells. Most importantly, RCA production in JH293-C21-C14-C28 cells was lower than in JH293-C21 cells. Conclusion: Human adenovirus producer cell clone JH293-C21-C14-C28 with CR2 deletion can effectively prevent the RCA production of replication-competent oncolytic adenovirus; this will provide significant advantages in utility and safety in gene therapy. Full article
(This article belongs to the Special Issue Oncolytic Viruses: A Key Step toward Cancer Immunotherapy)
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12 pages, 2911 KiB  
Article
High-Pressure Delivery of Oncolytic Viruses via Needle-Free Injection Preserves Therapeutic Activity
by Aida Said, Huy-Dung Hoang, Nathalie Earl, Xiao Xiang, Nadeem Siddiqui, Marceline Côté and Tommy Alain
Cancers 2023, 15(23), 5655; https://doi.org/10.3390/cancers15235655 - 30 Nov 2023
Viewed by 1297
Abstract
Intratumoural delivery of oncolytic viruses (OVs) to solid tumours is currently performed via multiple percutaneous methods of needle injections (NI). In this study, we investigated the potential use of a novel delivery approach, needle-free injection (NFI), to administer OVs to subcutaneous tumours. The [...] Read more.
Intratumoural delivery of oncolytic viruses (OVs) to solid tumours is currently performed via multiple percutaneous methods of needle injections (NI). In this study, we investigated the potential use of a novel delivery approach, needle-free injection (NFI), to administer OVs to subcutaneous tumours. The stability and genetic integrity of several RNA and DNA viruses exposed to high-pressure jet injectors were first evaluated in vitro. We demonstrate that replication competence and infectivity of the viruses remained unchanged after NFI, as compared to traditional NI. Using the oncolytic Vesicular Stomatitis Virus expressing luciferase (VSVΔ51-Luc) in the syngeneic CT26 subcutaneous tumour model, we show that NFI administration not only successfully delivers infectious particles but also increases the dissemination of the virus within the tumour tissues when compared to NI. Furthermore, mice treated with VSVΔ51-Luc by NFI delivery showed similar reduction in tumour growth and survival compared to those with needle-administered virus. These results indicate that NFI represents a novel approach to administer and potentially increase the spread of OVs within accessible solid tumours, highlighting its usefulness in virotherapy. Full article
(This article belongs to the Special Issue Oncolytic Viruses: A Key Step toward Cancer Immunotherapy)
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13 pages, 3167 KiB  
Article
Dual-Armed Oncolytic Myxoma Virus Encoding IFN-γ and CD47 Promotes Lymphocyte Infiltration and Tumor Suppression of Syngeneic Murine Melanoma
by Jong Kyu Woo, Tae-Geuk Kim, Na Yeon Im, Ka-Yeon Son, Minhyeon Cho, Yeo Jin Jeong, Jeong-Im Hong, BoRim Kang, Gansukh Enkhtaivan, Nam-Hyuk Cho, Tommy Alain, Dong Guk Park and Yeon-Sook Lee
Cancers 2023, 15(19), 4703; https://doi.org/10.3390/cancers15194703 - 24 Sep 2023
Viewed by 1305
Abstract
Myxoma virus (MyxV) is a rabbit-specific poxvirus. However, its ability to selectively target tumor cells has established it as a safe and effective anticancer therapy. To strengthen its preclinical efficacy, transgenes that can prolong cancer cell infection and enhance anti-tumor effector functions are [...] Read more.
Myxoma virus (MyxV) is a rabbit-specific poxvirus. However, its ability to selectively target tumor cells has established it as a safe and effective anticancer therapy. To strengthen its preclinical efficacy, transgenes that can prolong cancer cell infection and enhance anti-tumor effector functions are currently being investigated. We engineered MyxV armed with CD47, to turn on a ‘do not eat me’ signal within infected cells with actively replicating viruses, and with IFN-γ to further activate host immune anticancer responses. Tumor suppressive activities were significantly enhanced by the dual-armed MyxV_CD47/IFN-γ compared to parental MyxV or single-armed MyxV_CD47 or MyxV_IFN-γ. In addition, significant increases in IFN-γ+ CD8+T-cells and CD4+ T-cells populations within tumor-infiltrating lymphocytes (TIL) were observed after MyxV_CD47/IFN-γ treatment. Notably, all groups treated with MyxV showed a marked reduction in Foxp3+ CD4+ regulatory T-cells (Tregs) within TIL. We also show that MyxV infection induces PD-L1 up-regulation in cancer cells, and combinational treatment of MyxV with anti-mouse PD-L1 antibodies (αPD-L1) further controlled tumor burden and increased survival in the syngeneic melanoma model B16F10. Our data demonstrate that a CD47 and IFNγ dual-armed MyxV is an effective oncolytic viral immunotherapeutic. These findings strongly support further preclinical investigations to develop next-generation MyxV-based immunotherapy approaches. Full article
(This article belongs to the Special Issue Oncolytic Viruses: A Key Step toward Cancer Immunotherapy)
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19 pages, 6809 KiB  
Article
2-Deoxyglucose, an Inhibitor of Glycolysis, Enhances the Oncolytic Effect of Coxsackievirus
by Pavel O. Vorobyev, Dmitry V. Kochetkov, Peter M. Chumakov, Natalia F. Zakirova, Sofia I. Zotova-Nefedorova, Konstantin V. Vasilenko, Olga N. Alekseeva, Sergey N. Kochetkov, Birke Bartosch, Anastasiya V. Lipatova and Alexander V. Ivanov
Cancers 2022, 14(22), 5611; https://doi.org/10.3390/cancers14225611 - 15 Nov 2022
Cited by 5 | Viewed by 2098
Abstract
Glioblastoma multiforme (GBM) is one of the most common types of brain tumor. Despite intensive research, patients with GBM have a poor prognosis due to a very high rate of relapse and significant side effects of the treatment, with a median survival of [...] Read more.
Glioblastoma multiforme (GBM) is one of the most common types of brain tumor. Despite intensive research, patients with GBM have a poor prognosis due to a very high rate of relapse and significant side effects of the treatment, with a median survival of 14.6 months. Oncolytic viruses are considered a promising strategy to eliminate GBM and other types of cancer, and several viruses have already been introduced into clinical practice. However, identification of the factors that underly the sensitivity of tumor species to oncolytic viruses or that modulate their clinical efficacy remains an important target. Here, we show that Coxsackievirus B5 (CVB5) demonstrates high oncolytic potential towards GBM primary cell species and cell lines. Moreover, 2-deoxyglucose (2DG), an inhibitor of glycolysis, potentiates the cytopathic effects of CVB5 in most of the cancer cell lines tested. The cells in which the inhibition of glycolysis enhanced oncolysis are characterized by high mitochondrial respiratory activity and glycolytic capacity, as determined by Seahorse analysis. Thus, 2-deoxyglucose and other analogs should be considered as adjuvants for oncolytic therapy of glioblastoma multiforme. Full article
(This article belongs to the Special Issue Oncolytic Viruses: A Key Step toward Cancer Immunotherapy)
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