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Viruses
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Oncolytic Viruses as Immunotherapeutic Agents
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Oncolytic Viruses as Immunotherapeutic Agents

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: closed (1 May 2024) | Viewed by 16457

Special Issue Editor

Dr. Nadine Van Montfoort

E-Mail Website
Guest Editor
Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Interests: oncolytic viruses; cancer immunotherapy; innate immunity; adaptive immunity

Special Issue Information

Dear Colleagues,

In these challenging times, where pathogenic viruses such as SARS-CoV2 are at the center of attention, it is important to provide a platform for viruses that can help in treating cancer. These oncolytic viruses are non-pathogenic but instead they have the unique ability to specifically counteract malignant cells. One of the key features of oncolytic viruses is that they can create an immune-stimulatory inflammation in the tumor micro-environment. Therefore, oncolytic virotherapy can be classified as a novel type of targeted immunotherapy. An increasing amount of data suggests that oncolytic viruses can enhance efficacy of immunotherapy in resistant tumors. Still, many questions remain unanswered.

In this Special Issue, we will focus on understanding those mechanistic aspects needed to accelerate the development of this field. We welcome original studies and reviews about oncolytic virus-host immune interactions, viro-immunotherapy mechanisms, and novel combinatorial approaches

Dr. Nadine Van Montfoort
Guest Editor

Manuscript Submission Information

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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

  • oncolytic virus
  • oncolytic virotherapy
  • immunotherapy
  • cancer
  • tumor microenvironment

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Published Papers (7 papers)

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Research

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18 pages, 3068 KiB  
Article
Multimodal Therapy Approaches for NUT Carcinoma by Dual Combination of Oncolytic Virus Talimogene Laherparepvec with Small Molecule Inhibitors
by Stavros Sotiriadis, Julia Beil, Susanne Berchtold, Irina Smirnow, Andrea Schenk and Ulrich M. Lauer
Viruses 2024, 16(5), 775; https://doi.org/10.3390/v16050775 - 14 May 2024
Viewed by 1441
Abstract
NUT (nuclear-protein-in-testis) carcinoma (NC) is a highly aggressive tumor disease. Given that current treatment regimens offer a median survival of six months only, it is likely that this type of tumor requires an extended multimodal treatment approach to improve prognosis. In an earlier [...] Read more.
NUT (nuclear-protein-in-testis) carcinoma (NC) is a highly aggressive tumor disease. Given that current treatment regimens offer a median survival of six months only, it is likely that this type of tumor requires an extended multimodal treatment approach to improve prognosis. In an earlier case report, we could show that an oncolytic herpes simplex virus (T-VEC) is functional in NC patients. To identify further combination partners for T-VEC, we have investigated the anti-tumoral effects of T-VEC and five different small molecule inhibitors (SMIs) alone and in combination in human NC cell lines. Dual combinations were found to result in higher rates of tumor cell reductions when compared to the respective monotherapy as demonstrated by viability assays and real-time tumor cell growth monitoring. Interestingly, we found that the combination of T-VEC with SMIs resulted in both stronger and earlier reductions in the expression of c-Myc, a main driver of NC cell proliferation, when compared to T-VEC monotherapy. These results indicate the great potential of combinatorial therapies using oncolytic viruses and SMIs to control the highly aggressive behavior of NC cancers and probably will pave the way for innovative multimodal clinical studies in the near future. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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23 pages, 4340 KiB  
Article
The NDV-MLS as an Immunotherapeutic Strategy for Breast Cancer: Proof of Concept in Female Companion Dogs with Spontaneous Mammary Cancer
by Diana Sánchez, Gabriela Cesarman-Maus, Laura Romero, Rogelio Sánchez-Verin, David Vail, Marina Guadarrama, Rosana Pelayo, Rosa Elena Sarmiento-Silva and Marcela Lizano
Viruses 2024, 16(3), 372; https://doi.org/10.3390/v16030372 - 28 Feb 2024
Cited by 1 | Viewed by 1990
Abstract
The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease [...] Read more.
The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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18 pages, 3810 KiB  
Article
Oncolytic Efficacy of a Recombinant Vaccinia Virus Strain Expressing Bacterial Flagellin in Solid Tumor Models
by Yasmin Shakiba, Pavel O. Vorobyev, Victor A. Naumenko, Dmitry V. Kochetkov, Ksenia V. Zajtseva, Marat P. Valikhov, Gaukhar M. Yusubalieva, Yana D. Gumennaya, Egor A. Emelyanov, Alevtina S. Semkina, Vladimir P. Baklaushev, Peter M. Chumakov and Anastasia V. Lipatova
Viruses 2023, 15(4), 828; https://doi.org/10.3390/v15040828 - 24 Mar 2023
Cited by 6 | Viewed by 2860
Abstract
Oncolytic viral therapy is a promising novel approach to cancer treatment. Oncolytic viruses cause tumor regression through direct cytolysis on the one hand and recruiting and activating immune cells on the other. In this study, to enhance the antitumor efficacy of the thymidine [...] Read more.
Oncolytic viral therapy is a promising novel approach to cancer treatment. Oncolytic viruses cause tumor regression through direct cytolysis on the one hand and recruiting and activating immune cells on the other. In this study, to enhance the antitumor efficacy of the thymidine kinase-deficient vaccinia virus (VV, Lister strain), recombinant variants encoding bacterial flagellin (subunit B) of Vibrio vulnificus (LIVP-FlaB-RFP), firefly luciferase (LIVP-Fluc-RFP) or red fluorescent protein (LIVP-RFP) were developed. The LIVP-FLuc-RFP strain demonstrated exceptional onco-specificity in tumor-bearing mice, detected by the in vivo imaging system (IVIS). The antitumor efficacy of these variants was explored in syngeneic murine tumor models (B16 melanoma, CT26 colon cancer and 4T1 breast cancer). After intravenous treatment with LIVP-FlaB-RFP or LIVP-RFP, all mice tumor models exhibited tumor regression, with a prolonged survival rate in comparison with the control mice. However, superior oncolytic activity was observed in the B16 melanoma models treated with LIVP-FlaB-RFP. Tumor-infiltrated lymphocytes and the cytokine analysis of the serum and tumor samples from the melanoma-xenografted mice treated with these virus variants demonstrated activation of the host’s immune response. Thus, the expression of bacterial flagellin by VV can enhance its oncolytic efficacy against immunosuppressive solid tumors. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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18 pages, 7254 KiB  
Article
Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model
by Jana Koch, Julia Beil, Susanne Berchtold, Dina Mönch, Annika Maaß, Irina Smirnow, Andrea Schenk, Mary E. Carter, Linus D. Kloker, Tobias Leibold, Philipp Renner, Marc-H. Dahlke and Ulrich M. Lauer
Viruses 2023, 15(2), 363; https://doi.org/10.3390/v15020363 - 27 Jan 2023
Cited by 1 | Viewed by 2009
Abstract
Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines [...] Read more.
Oncolytic virotherapy constitutes a promising treatment option for many solid cancers, including peritoneal carcinomatosis (PC), which still represents a terminal stage of many types of tumors. To date, the in vitro efficacy of oncolytic viruses is mostly tested in 2D-cultured tumor cell lines due to the lack of realistic 3D in vitro tumor models. We have investigated the feasibility of virotherapy as a treatment option for PC in a human ex vivo peritoneum co-culture model. Human HT-29 cancer cells stably expressing marker genes GFP and firefly luciferase (GFP/luc) were cultured on human peritoneum and infected with two prototypic oncolytic viruses (GLV-0b347 and MeV-DsRed). Both viral constructs were able to infect HT-29 cells in patient-derived peritoneum with high tumor specificity. Over time, both GFP signal and luciferase activity decreased substantially, thereby indicating successful virus-induced oncolysis. Furthermore, immunohistochemistry stainings showed specific virotherapeutic infections of HT-29 cells and effective tumor cell lysis in infected co-cultures. Thus, the PC model established here provides a clinically relevant screening platform to evaluate the therapeutic efficacy of virotherapeutic compounds and also to investigate, in an autologous setting, the immunostimulatory potential of oncolytic viruses for PC in a unique human model system superior to standard 2D in vitro models. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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17 pages, 2152 KiB  
Article
Histone Deacetylase Inhibitor Panobinostat Benefits the Therapeutic Efficacy of Oncolytic Herpes Simplex Virus Combined with PD-1/PD-L1 Blocking in Glioma and Squamous Cell Carcinoma Models
by Yinglin Wu, Xiaoqing Chen, Lei Wang, Xusha Zhou, Yonghong Liu, Dongmei Ji, Peigen Ren, Grace Guoying Zhou and Jing Zhao
Viruses 2022, 14(12), 2796; https://doi.org/10.3390/v14122796 - 15 Dec 2022
Cited by 3 | Viewed by 2370
Abstract
Background: Combination therapy has been widely explored for oncolytic virus (OV), as it can be met with tumor resistance. The HDAC inhibitor (HDACi) panobinostat is a potent pan-deacetylase inhibitor which blocks multiple cancer-related pathways and reverses epigenetic events in cancer progression. Methods: In [...] Read more.
Background: Combination therapy has been widely explored for oncolytic virus (OV), as it can be met with tumor resistance. The HDAC inhibitor (HDACi) panobinostat is a potent pan-deacetylase inhibitor which blocks multiple cancer-related pathways and reverses epigenetic events in cancer progression. Methods: In this study, oncolytic activity in vitro and antitumor therapeutic efficacy in vivo when combined with oHSV and panobinostat were investigated. Results: (1) Treatment with panobinostat enhanced oHSV propagation and cytotoxicity in human glioma A172 and squamous cell carcinoma SCC9 cells. (2) Combined treatment with oHSV and panobinostat enhanced virus replication mediated by the transcriptional downregulation of IFN-β- and IFN-responsive antiviral genes in human glioma A172 and squamous cell carcinoma SCC9 cells. (3) Panobinostat treatment induced upregulation of PD-L1 expression in both glioma and squamous cell carcinoma cells. (4) A significantly enhanced therapeutic efficacy was shown in vivo for the murine glioma CT-2A and squamous cell carcinoma SCC7 models when treated with a combination of oHSV, including PD-1/PD-L1 blockade and HDAC inhibition. Conclusions: Consequently, these data provide some new clues for the clinical development of combination therapy with OVs, epigenetic modifiers, and checkpoint blockades for glioma and squamous cell carcinoma. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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Review

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10 pages, 578 KiB  
Review
Oncolytic Viral Therapy in Osteosarcoma
by Thomas Karadimas, Thien Huong Huynh, Chloe Chose, Guston Zervoudakis, Bryan Clampitt, Sean Lapp, David Joyce, George Douglas Letson, Jonathan Metts, Odion Binitie, John E. Mullinax and Alexander Lazarides
Viruses 2024, 16(7), 1139; https://doi.org/10.3390/v16071139 - 16 Jul 2024
Viewed by 1221
Abstract
Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring [...] Read more.
Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring or genetically modified viruses to selectively target and lyse cancer cells and induce a robust immune response against remaining OS cells. Various oncolytic viruses (OVs), such as adenovirus, herpes simplex virus, and measles virus, have demonstrated efficacy in preclinical OS models. Combining OVT with other therapeutics, such as chemotherapy or immunotherapy, may further improve outcomes. Despite these advances, challenges in reliability of preclinical models, safety, delivery, and immune response must be addressed to optimize OVT for clinical use. Future research should focus on refining delivery methods, exploring combination treatments, and clinical trials to ensure OVT’s efficacy and safety for OS. Overall, OVT represents a novel approach with the potential to drastically improve survival outcomes for patients with OS. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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24 pages, 2373 KiB  
Review
Oncolytic Virus Engineering and Utilizations: Cancer Immunotherapy Perspective
by Palaniyandi Muthukutty and So Young Yoo
Viruses 2023, 15(8), 1645; https://doi.org/10.3390/v15081645 - 28 Jul 2023
Cited by 16 | Viewed by 3315
Abstract
Oncolytic viruses have positively impacted cancer immunotherapy over the past 20 years. Both natural and genetically modified viruses have shown promising results in treating various cancers. Various regulatory authorities worldwide have approved four commercial oncolytic viruses, and more are being developed to overcome [...] Read more.
Oncolytic viruses have positively impacted cancer immunotherapy over the past 20 years. Both natural and genetically modified viruses have shown promising results in treating various cancers. Various regulatory authorities worldwide have approved four commercial oncolytic viruses, and more are being developed to overcome this limitation and obtain better anti-tumor responses in clinical trials at various stages. Faster advancements in translating research into the commercialization of cancer immunotherapy and a comprehensive understanding of the modification strategies will widen the current knowledge of future technologies related to the development of oncolytic viruses. In this review, we discuss the strategies of virus engineering and the progress of clinical trials to achieve virotherapeutics. Full article
(This article belongs to the Special Issue Oncolytic Viruses as Immunotherapeutic Agents)
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