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Oncolytic Viruses for Cancer Immunotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 5706

Special Issue Editor


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Guest Editor
Department Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands
Interests: cancer therapy development; therapeutic target discovery; functional genetic screening; oncolytic immunotherapy
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Special Issue Information

Dear Colleagues,

Oncolytic viruses are considered powerful additions to the arsenal of anticancer agents. They are unique in their combined activities of inducing selective cancer cell killing, propagating and self-amplifying in solid tumors and promoting anti-tumor immune responses. In recent years, several important improvements in oncolytic virus design and delivery methods were made to enhance their safety and efficacy for cancer treatment. Furthermore, mechanistic studies deepened our understanding of how oncolytic viruses work within the tumor microenvironment. Promising results from clinical trials and the first granted market approvals for oncolytic-virus-based cancer therapies underscore the growing recognition of oncolytic immunotherapy as a viable option for treating cancer.

This Special Issue of IJMS intends to provide an overview of the latest advances in the field and to present innovations driving the field forward, as well as studies addressing challenges encountered in applying oncolytic viruses in cancer treatment. Authors are invited to submit original research and review articles, particularly those on the following topics:

  • Molecular design of oncolytic viruses, with improved specificity or infectivity.
  • Modification of virus capsid proteins and encapsulation technologies to prolong in vivo stability and reduce neutralization.
  • Arming oncolytic viruses to create more potent anticancer agents, expressing transgenes to enforce cancer cell killing potency, replication speed, tissue dispersion, or immune response.
  • The use of non-human viruses and not yet widely explored viruses or virus strains as oncolytic agents.
  • Investigation of immune response modulation by oncolytic viruses in the tumor microenvironment.
  • Relevant preclinical models for studying the efficacy of oncolytic immunotherapy treatment.
  • Discovery of predictive biomarkers for susceptibility to oncolytic virus treatment.
  • Assays to monitor biological effects of oncolytic viruses on preclinical models.
  • Advanced methods for local and systemic delivery, including the use of controlled release formulations or cellular vehicles.
  • Combination studies on oncolytic viruses and immune-modulating compounds or cancer-targeted immune cells to optimize adaptive antitumor immune responses.

Prof. Dr. Victor van Beusechem
Guest Editor

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Keywords

  • oncolytic viruses
  • anti-tumor immune responses
  • oncolytic immunotherapy

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Published Papers (4 papers)

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Research

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16 pages, 2961 KiB  
Article
Quantitative Virus-Associated RNA Detection to Monitor Oncolytic Adenovirus Replication
by Tereza Brachtlova, Jing Li, Ida H. van der Meulen-Muileman, Femke Sluiter, Willem von Meijenfeldt, Isabella Witte, Sanne Massaar, Ruben van den Oever, Jeroen de Vrij and Victor W. van Beusechem
Int. J. Mol. Sci. 2024, 25(12), 6551; https://doi.org/10.3390/ijms25126551 - 14 Jun 2024
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Abstract
Oncolytic adenoviruses are in development as immunotherapeutic agents for solid tumors. Their efficacy is in part dependent on their ability to replicate in tumors. It is, however, difficult to obtain evidence for intratumoral oncolytic adenovirus replication if direct access to the tumor is [...] Read more.
Oncolytic adenoviruses are in development as immunotherapeutic agents for solid tumors. Their efficacy is in part dependent on their ability to replicate in tumors. It is, however, difficult to obtain evidence for intratumoral oncolytic adenovirus replication if direct access to the tumor is not possible. Detection of systemic adenovirus DNA, which is sometimes used as a proxy, has limited value because it does not distinguish between the product of intratumoral replication and injected virus that did not replicate. Therefore, we investigated if detection of virus-associated RNA (VA RNA) by RT-qPCR on liquid biopsies could be used as an alternative. We found that VA RNA is expressed in adenovirus-infected cells in a replication-dependent manner and is secreted by these cells in association with extracellular vesicles. This allowed VA RNA detection in the peripheral blood of a preclinical in vivo model carrying adenovirus-injected human tumors and on liquid biopsies from a human clinical trial. Our results confirm that VA RNA detection in liquid biopsies can be used for minimally invasive assessment of oncolytic adenovirus replication in solid tumors in vivo. Full article
(This article belongs to the Special Issue Oncolytic Viruses for Cancer Immunotherapy)
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15 pages, 1879 KiB  
Article
The Recombinant Oncolytic Virus VV-GMCSF-Lact and Chemotherapy Drugs against Human Glioma
by Natalia Vasileva, Alisa Ageenko, Arina Byvakina, Aleksandra Sen’kova, Galina Kochneva, Sergey Mishinov, Vladimir Richter and Elena Kuligina
Int. J. Mol. Sci. 2024, 25(8), 4244; https://doi.org/10.3390/ijms25084244 - 11 Apr 2024
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Abstract
Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different [...] Read more.
Virotherapy is one of the perspective technologies in the treatment of malignant neoplasms. Previously, we have developed oncolytic vaccinia virus VV-GMCSF-Lact and its high cytotoxic activity and antitumor efficacy against glioma was shown. In this work, using immortalized and patient-derived cells with different sensitivity to VV-GMCSF-Lact, we evaluated the cytotoxic effect of chemotherapy agents. Additionally, we studied the combination of VV-GMCSF-Lact with temozolomide which is the most preferred drug for glioma treatment. Experimental results indicate that first adding temozolomide and then the virus to the cells is inherently more efficient than dosing it in the reverse order. Testing these regimens in the U87 MG xenograft glioblastoma model confirmed this effect, as assessed by tumor growth inhibition index and histological analysis. Moreover, VV-GMCSF-Lact as monotherapy is more effective against U87 MG glioblastoma xenografts comparing temozolomide. Full article
(This article belongs to the Special Issue Oncolytic Viruses for Cancer Immunotherapy)
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Review

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28 pages, 3228 KiB  
Review
OV Modulators of the Paediatric Brain TIME: Current Status, Combination Strategies, Limitations and Future Directions
by Konstantinos Vazaios, Ronja E. van Berkum, Friso G. Calkoen, Jasper van der Lugt and Esther Hulleman
Int. J. Mol. Sci. 2024, 25(9), 5007; https://doi.org/10.3390/ijms25095007 - 3 May 2024
Viewed by 1451
Abstract
Oncolytic viruses (OVs) are characterised by their preference for infecting and replicating in tumour cells either naturally or after genetic modification, resulting in oncolysis. Furthermore, OVs can elicit both local and systemic anticancer immune responses while specifically infecting and lysing tumour cells. These [...] Read more.
Oncolytic viruses (OVs) are characterised by their preference for infecting and replicating in tumour cells either naturally or after genetic modification, resulting in oncolysis. Furthermore, OVs can elicit both local and systemic anticancer immune responses while specifically infecting and lysing tumour cells. These characteristics render them a promising therapeutic approach for paediatric brain tumours (PBTs). PBTs are frequently marked by a cold tumour immune microenvironment (TIME), which suppresses immunotherapies. Recent preclinical and clinical studies have demonstrated the capability of OVs to induce a proinflammatory immune response, thereby modifying the TIME. In-depth insights into the effect of OVs on different cell types in the TIME may therefore provide a compelling basis for using OVs in combination with other immunotherapy modalities. However, certain limitations persist in our understanding of oncolytic viruses’ ability to regulate the TIME to enhance anti-tumour activity. These limitations primarily stem from the translational limitations of model systems, the difficulties associated with tracking reliable markers of efficacy throughout the course of treatment and the role of pre-existing viral immunity. In this review, we describe the different alterations observed in the TIME in PBTs due to OV treatment, combination therapies of OVs with different immunotherapies and the hurdles limiting the development of effective OV therapies while suggesting future directions based on existing evidence. Full article
(This article belongs to the Special Issue Oncolytic Viruses for Cancer Immunotherapy)
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16 pages, 1428 KiB  
Review
Molecular Circuits of Immune Sensing and Response to Oncolytic Virotherapy
by Darshak K. Bhatt and Toos Daemen
Int. J. Mol. Sci. 2024, 25(9), 4691; https://doi.org/10.3390/ijms25094691 - 25 Apr 2024
Viewed by 1207
Abstract
Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to [...] Read more.
Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy, focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated-signal sensing by neighboring cells, and the subsequent downstream activation of immune pathways. These sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how the molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting-cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies. Full article
(This article belongs to the Special Issue Oncolytic Viruses for Cancer Immunotherapy)
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