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Viruses
Special Issues
Progress and Prospects in Oncolytic Virotherapy
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Progress and Prospects in Oncolytic Virotherapy

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 5865

Special Issue Editors

Dr. Arianna Calistri

E-Mail Website
Guest Editor
Department of Molecular Medicine, University of Padua, Padova, Italy
Interests: virus–host interactions; viral vectors; oncovirotherapy; antiviral strategies
Dr. Sandra Tuyaerts

E-Mail Website
Guest Editor
Gynaecological Oncology, KU Leuven, 3000 Leuven, Belgium
Interests: cancer immunology and immunotherapy; tumor antigens; drug repurposing

Special Issue Information

Dear Colleagues,

Oncovirotherapy is a very promising strategy to tackle tumors based on viruses that either naturally or upon specific manipulations display direct cancer-cell-killing activity along with immunotherapeutic effects. Although a growing number of clinical studies clearly demonstrate the excellent safety profile of oncolytic viruses, to date, only the HSV-1 talimogene laherparepvec (T-Vec) has been approved in the USA and Europe for the treatment of unresectable melanoma. One of the reasons for the limited approval of oncolytic viruses can be found in their adoption as monotherapy in most of the clinical trials performed so far, often resulting in poor efficacy. This Special Issue aims to present readers with the latest developments and challenges in the field of oncolytic virus research. Additionally, we aim to evaluate the therapeutic possibilities of integrating oncovirotherapy with chemotherapy or immunotherapy.

Dr. Arianna Calistri
Dr. Sandra Tuyaerts
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • oncovirotherapy
  • chemotherapy
  • preclinical studies
  • clinical trials
  • combinatory strategy
  • safety profile
  • therapeutic efficacy
  • immunotherapy

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Published Papers (4 papers)

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Research

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14 pages, 6744 KiB  
Article
Differential Replication and Oncolytic Effects of Zika Virus in Aggressive CNS Tumor Cells: Insights from Organoid and Tumoroid Models
by Rodolfo Sanches Ferreira, Elisa Helena Farias Jandrey, Isabela Granha, Alice Kei Endo, Raiane Oliveira Ferreira, Bruno Henrique Silva Araujo, Mayana Zatz and Oswaldo Keith Okamoto
Viruses 2024, 16(11), 1764; https://doi.org/10.3390/v16111764 - 12 Nov 2024
Viewed by 750
Abstract
Central nervous system (CNS) cancers are responsible for high rates of morbidity and mortality worldwide. Malignant CNS tumors such as adult Glioblastoma (GBM) and pediatric embryonal CNS tumors such as medulloblastoma (MED) and atypical teratoid rhabdoid tumors (ATRT) present relevant therapeutic challenges due [...] Read more.
Central nervous system (CNS) cancers are responsible for high rates of morbidity and mortality worldwide. Malignant CNS tumors such as adult Glioblastoma (GBM) and pediatric embryonal CNS tumors such as medulloblastoma (MED) and atypical teratoid rhabdoid tumors (ATRT) present relevant therapeutic challenges due to the lack of response to classic treatment regimens with radio and chemotherapy. Recent findings on the Zika virus’ (ZIKV) ability to infect and kill CNS neoplastic cells draw attention to the virus’ oncolytic potential. Studies demonstrating the safety of using ZIKV for treating malignant CNS tumors, enabling the translation of this approach to clinical trials, are scarce in the literature. Here we developed a co-culture model of mature human cerebral organoids assembled with GBM, MED or ATRT tumor cells and used these assembloids to test ZIKV oncolytic effect, replication potential and preferential targeting between normal and cancer cells. Our hybrid co-culture models allowed the tracking of tumor cell growth and invasion in cerebral organoids. ZIKV replication and ensuing accumulation in the culture medium was higher in organoids co-cultured with tumor cells than in isolated control organoids without tumor cells. ZIKV infection led to a significant reduction in tumor cell proportion in organoids with GBM and MED cells, but not with ATRT. Tumoroids (3D cultures of tumor cells alone) were efficiently infected by ZIKV. Interestingly, ZIKV rapidly replicated in GBM, MED, and ATRT tumoroids reaching significantly higher viral RNA accumulation levels than co-cultures. Moreover, ZIKV infection reduced viable cells number in MED and ATRT tumoroids but not in GBM tumoroids. Altogether, our findings indicate that ZIKV has greater replication rates in aggressive CNS tumor cells than in normal human cells comprising cerebral organoids. However, such higher ZIKV replication in tumor cells does not necessarily parallels oncolytic effects, suggesting cellular intrinsic and extrinsic factors mediating tumor cell death by ZIKV. Full article
(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy)
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17 pages, 14024 KiB  
Article
Tepilamide Fumarate as a Novel Potentiator of Virus-Based Therapy
by Akram Alwithenani, Rozanne Arulanandam, Boaz Wong, Marcus M. Spinelli, Andrew Chen, Glib Maznyi, Victoria H. Gilchrist, Tommy Alain and Jean-Simon Diallo
Viruses 2024, 16(6), 920; https://doi.org/10.3390/v16060920 - 5 Jun 2024
Cited by 1 | Viewed by 1406
Abstract
Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis [...] Read more.
Oncolytic virotherapy, using viruses such as vesicular stomatitis virus (VSVΔ51) and Herpes Simplex Virus-1 (HSV-1) to selectively attack cancer cells, faces challenges such as cellular resistance mediated by the interferon (IFN) response. Dimethyl fumarate (DMF) is used in the treatment of multiple sclerosis and psoriasis and is recognized for its anti-cancer properties and has been shown to enhance both VSVΔ51 and HSV-1 oncolytic activity. Tepilamide fumarate (TPF) is a DMF analog currently undergoing clinical trials for the treatment of moderate-to-severe plaque psoriasis. The aim of this study was to evaluate the potential of TPF in enhancing the effectiveness of oncolytic viruses. In vitro, TPF treatment rendered 786-0 carcinoma cells more susceptible to VSVΔ51 infection, leading to increased viral replication. It outperformed DMF in both increasing viral infection and increasing the killing of these resistant cancer cells and other cancer cell lines tested. Ex vivo studies demonstrated TPF’s selective boosting of oncolytic virus infection in cancer cells without affecting healthy tissues. Effectiveness was notably high in pancreatic and ovarian tumor samples. Our study further indicates that TPF can downregulate the IFN pathway through a similar mechanism to DMF, making resistant cancer cells more vulnerable to viral infection. Furthermore, TPF’s impact on gene therapy was assessed, revealing its ability to enhance the transduction efficiency of vectors such as lentivirus, adenovirus type 5, and adeno-associated virus type 2 across various cell lines. This data underscore TPF’s potential role in not only oncolytic virotherapy but also in the broader application of gene therapy. Collectively, these findings position TPF as a promising agent in oncolytic virotherapy, warranting further exploration of its therapeutic potential. Full article
(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy)
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Review

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23 pages, 1586 KiB  
Review
Oncolytic Virotherapies and Adjuvant Gut Microbiome Therapeutics to Enhance Efficacy Against Malignant Gliomas
by Natalie M. Meléndez-Vázquez, Candelaria Gomez-Manzano and Filipa Godoy-Vitorino
Viruses 2024, 16(11), 1775; https://doi.org/10.3390/v16111775 - 14 Nov 2024
Viewed by 817
Abstract
Glioblastoma (GBM) is the most prevalent malignant brain tumor. Current standard-of-care treatments offer limited benefits for patient survival. Virotherapy is emerging as a novel strategy to use oncolytic viruses (OVs) for the treatment of GBM. These engineered and non-engineered viruses infect and lyse [...] Read more.
Glioblastoma (GBM) is the most prevalent malignant brain tumor. Current standard-of-care treatments offer limited benefits for patient survival. Virotherapy is emerging as a novel strategy to use oncolytic viruses (OVs) for the treatment of GBM. These engineered and non-engineered viruses infect and lyse cancer cells, causing tumor destruction without harming healthy cells. Recent advances in genetic modifications to OVs have helped improve their targeting capabilities and introduce therapeutic genes, broadening the therapeutic window and minimizing potential side effects. The efficacy of oncolytic virotherapy can be enhanced by combining it with other treatments such as immunotherapy, chemotherapy, or radiation. Recent studies suggest that manipulating the gut microbiome to enhance immune responses helps improve the therapeutic efficacy of the OVs. This narrative review intends to explore OVs and their role against solid tumors, especially GBM while emphasizing the latest technologies used to enhance and improve its therapeutic and clinical responses. Full article
(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy)
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15 pages, 2375 KiB  
Review
Zika Virus: A Neurotropic Warrior against High-Grade Gliomas—Unveiling Its Potential for Oncolytic Virotherapy
by María-Angélica Calderón-Peláez, Silvia Juliana Maradei Anaya, Ingrid Juliana Bedoya-Rodríguez, Karol Gabriela González-Ipuz, Daniela Vera-Palacios, Isabella Victoria Buitrago, Jaime E. Castellanos and Myriam L. Velandia-Romero
Viruses 2024, 16(4), 561; https://doi.org/10.3390/v16040561 - 3 Apr 2024
Cited by 1 | Viewed by 2115
Abstract
Gliomas account for approximately 75–80% of all malignant primary tumors in the central nervous system (CNS), with glioblastoma multiforme (GBM) considered the deadliest. Despite aggressive treatment involving a combination of chemotherapy, radiotherapy, and surgical intervention, patients with GBM have limited survival rates of [...] Read more.
Gliomas account for approximately 75–80% of all malignant primary tumors in the central nervous system (CNS), with glioblastoma multiforme (GBM) considered the deadliest. Despite aggressive treatment involving a combination of chemotherapy, radiotherapy, and surgical intervention, patients with GBM have limited survival rates of 2 to 5 years, accompanied by a significant decline in their quality of life. In recent years, novel management strategies have emerged, such as immunotherapy, which includes the development of vaccines or T cells with chimeric antigen receptors, and oncolytic virotherapy (OVT), wherein wild type (WT) or genetically modified viruses are utilized to selectively lyse tumor cells. In vitro and in vivo studies have shown that the Zika virus (ZIKV) can infect glioma cells and induce a robust oncolytic activity. Consequently, interest in exploring this virus as a potential oncolytic virus (OV) for high-grade gliomas has surged. Given that ZIKV actively circulates in Colombia, evaluating its neurotropic and oncolytic capabilities holds considerable national and international importance, as it may emerge as an alternative for treating highly complex gliomas. Therefore, this literature review outlines the generalities of GBM, the factors determining ZIKV’s specific tropism for nervous tissue, and its oncolytic capacity. Additionally, we briefly present the progress in preclinical studies supporting the use of ZIKV as an OVT for gliomas. Full article
(This article belongs to the Special Issue Progress and Prospects in Oncolytic Virotherapy)
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