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Oncolytic Virotherapy 2.0
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Oncolytic Virotherapy 2.0

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

Deadline for manuscript submissions: closed (26 August 2022) | Viewed by 35099

Special Issue Editor

Dr. Laura Menotti

E-Mail Website
Guest Editor
Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy
Interests: oncolytic herpes simplex virus; tropism retargeting; cancer receptors; virus engineering; virus arming; virus-mediated transgene expression
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent years have seen tremendous advances in cancer diagnosis, profiling and therapy. However, some types of tumors are still a scourge on society, due to the limited efficacy of traditional chemo/radiotherapy treatments, and in some cases, the restricted possibilities of surgical intervention at the primary tumor site, or the impossibility to block, access or destroy metastases. A new generation of biological therapeutics is emerging, and promises to tackle these demanding aspects of cancer. In this scenario, oncolytic viruses (OVs) offer exciting possibilities: the first registered OV, licensed for the treatment of metastatic melanoma, belongs to the herpesviridae family, and other members of different virus families are in the pipeline. The great effort at the preclinical research stage put into these advanced anti-cancer strategies pledge important breakthroughs in this challenging field, to get more oncolytic viruses from the bench to the bedside. In this regard, submissions of original research papers, perspectives and reviews are welcome for this Special Issue. Topics of interest include, but are not limited to:

oncolytic virus design and engineering

oncolytic virus retargeting, shielding, arming

viral delivery of therapeutic proteins

cancer gene therapy

cancer imaging

oncolytic virus delivery

systemic virotherapy

cancer treatment

metastases targeting

combination therapies

viro-immunotherapy and neoadjuvant treatment

animal models for oncolytic virotherapy

Prof. Laura Menotti
Guest Editor

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Keywords

  • oncolytic virus
  • viro-immunotherapy
  • oncolytic virotherapy
  • cancer gene therapy

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Published Papers (13 papers)

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Research

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21 pages, 3921 KiB  
Article
Inhibition of Bromodomain Proteins Enhances Oncolytic HAdVC5 Replication and Efficacy in Pancreatic Ductal Adenocarcinoma (PDAC) Models
by Tizong Miao, Alistair Symonds, Oliver J. Hickman, Dongsheng Wu, Ping Wang, Nick Lemoine, Yaohe Wang, Spiros Linardopoulos and Gunnel Halldén
Int. J. Mol. Sci. 2024, 25(2), 1265; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25021265 - 19 Jan 2024
Viewed by 1034
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of pancreatic cancer, which rapidly develops resistance to the current standard of care. Several oncolytic Human AdenoViruses (HAdVs) have been reported to re-sensitize drug-resistant cancer cells and in combination with chemotherapeutics attenuate solid tumour [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive type of pancreatic cancer, which rapidly develops resistance to the current standard of care. Several oncolytic Human AdenoViruses (HAdVs) have been reported to re-sensitize drug-resistant cancer cells and in combination with chemotherapeutics attenuate solid tumour growth. Obstacles preventing greater clinical success are rapid hepatic elimination and limited viral replication and spread within the tumour microenvironment. We hypothesised that higher intratumoural levels of the virus could be achieved by altering cellular epigenetic regulation. Here we report on the screening of an enriched epigenetics small molecule library and validation of six compounds that increased viral gene expression and replication. The greatest effects were observed with three epigenetic inhibitors targeting bromodomain (BRD)-containing proteins. Specifically, BRD4 inhibitors enhanced the efficacy of Ad5 wild type, Ad∆∆, and Ad-3∆-A20T in 3-dimensional co-culture models of PDAC and in vivo xenografts. RNAseq analysis demonstrated that the inhibitors increased viral E1A expression, altered expression of cell cycle regulators and inflammatory factors, and attenuated expression levels of tumour cell oncogenes such as c-Myc and Myb. The data suggest that the tumour-selective Ad∆∆ and Ad-3∆-A20T combined with epigenetic inhibitors is a novel strategy for the treatment of PDAC by eliminating both cancer and associated stromal cells to pave the way for immune cell access even after systemic delivery of the virus. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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11 pages, 1640 KiB  
Article
Treatment of HPV-Related Uterine Cervical Cancer with a Third-Generation Oncolytic Herpes Simplex Virus in Combination with an Immune Checkpoint Inhibitor
by Masahiro Kagabu, Naoto Yoshino, Kazuyuki Murakami, Hideki Kawamura, Yutaka Sasaki, Yasushi Muraki and Tsukasa Baba
Int. J. Mol. Sci. 2023, 24(3), 1988; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24031988 - 19 Jan 2023
Cited by 3 | Viewed by 1773
Abstract
Cervical cancer is one of the most common cancers in women. The development of new therapies with immune checkpoint inhibitors (ICIs) is being investigated for cervical cancer; however, their efficacy is not currently sufficient. Oncolytic virus therapy can increase tumor immunogenicity and enhance [...] Read more.
Cervical cancer is one of the most common cancers in women. The development of new therapies with immune checkpoint inhibitors (ICIs) is being investigated for cervical cancer; however, their efficacy is not currently sufficient. Oncolytic virus therapy can increase tumor immunogenicity and enhance the antitumor effect of ICIs. In this report, the therapeutic potential of a triple-mutated oncolytic herpes virus (T-01) with an ICI for human papillomavirus (HPV)-related cervical cancer was evaluated using a bilateral syngeneic murine model. The efficacy of intratumoral (i.t.) administration with T-01 and subcutaneous (s.c.) administration of anti-programmed cell death ligand 1 (PD-L1) antibody (Ab) was equivalent to that of anti-PD-L1 Ab alone on the T-01-injected side. Moreover, combination therapy had no significant antitumor effect compared to monotherapy on the T-01-non-injected side. Combination therapy significantly increased the number of tumor specific T cells in the tumor. While T-01 could not be isolated from tumors receiving combination therapy, it could be isolated following T-01 monotherapy. Furthermore, T-01 had a cytotoxic effect on stimulated T cells. These results suggest that T-01 and anti-PD-L1 Ab partially counteract and therefore concomitant administration should be considered with caution. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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19 pages, 5226 KiB  
Article
The Oncolytic Adenovirus XVir-N-31, in Combination with the Blockade of the PD-1/PD-L1 Axis, Conveys Abscopal Effects in a Humanized Glioblastoma Mouse Model
by Moritz Klawitter, Ali El-Ayoubi, Jasmin Buch, Jakob Rüttinger, Maximilian Ehrenfeld, Eva Lichtenegger, Marcel A. Krüger, Klaus Mantwill, Florestan J. Koll, Markus C. Kowarik, Per Sonne Holm and Ulrike Naumann
Int. J. Mol. Sci. 2022, 23(17), 9965; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179965 - 01 Sep 2022
Cited by 10 | Viewed by 2540
Abstract
Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is [...] Read more.
Glioblastoma (GBM) is an obligatory lethal brain tumor with a median survival, even with the best standard of care therapy, of less than 20 months. In light of this fact, the evaluation of new GBM treatment approaches such as oncolytic virotherapy (OVT) is urgently needed. Based on our preliminary preclinical data, the YB-1 dependent oncolytic adenovirus (OAV) XVir-N-31 represents a promising therapeutic agent to treat, in particular, therapy resistant GBM. Preclinical studies have shown that XVir-N-31 prolonged the survival of GBM bearing mice. Now using an immunohumanized mouse model, we examined the immunostimulatory effects of XVir-N-31 in comparison to the wildtype adenovirus (Ad-WT). Additionally, we combined OVT with the inhibition of immune checkpoint proteins by using XVir-N-31 in combination with nivolumab, or by using a derivate of XVir-N-31 that expresses a PD-L1 neutralizing antibody. Although in vitro cell killing was higher for Ad-WT, XVir-N-31 induced a much stronger immunogenic cell death that was further elevated by blocking PD-1 or PD-L1. In vivo, an intratumoral injection of XVir-N-31 increased tumor infiltrating lymphocytes (TILs) and NK cells significantly more than Ad-WT not only in the virus-injected tumors, but also in the untreated tumors growing in the contralateral hemisphere. This suggests that for an effective treatment of GBM, immune activating properties by OAVs seem to be of greater importance than their oncolytic capacity. Furthermore, the addition of immune checkpoint inhibition (ICI) to OVT further induced lymphocyte infiltration. Consequently, a significant reduction in contralateral non-virus-injected tumors was only visible if OVT was combined with ICI. This strongly indicates that for an effective eradication of GBM cells that cannot be directly targeted by an intratumoral OV injection, additional ICI therapy is required. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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17 pages, 3798 KiB  
Article
Oncolytic Herpes Simplex Virus Type 1 Induces Immunogenic Cell Death Resulting in Maturation of BDCA-1+ Myeloid Dendritic Cells
by Philipp Kalus, Jolien De Munck, Sarah Vanbellingen, Laura Carreer, Thessa Laeremans, Katrijn Broos, Inès Dufait, Julia K. Schwarze, Ivan Van Riet, Bart Neyns, Karine Breckpot and Joeri L. Aerts
Int. J. Mol. Sci. 2022, 23(9), 4865; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094865 - 27 Apr 2022
Cited by 10 | Viewed by 2269
Abstract
Recently, a paradigm shift has been established for oncolytic viruses (OVs) as it was shown that the immune system plays an important role in the specific killing of tumor cells by OVs. OVs have the intrinsic capacity to provide the right signals to [...] Read more.
Recently, a paradigm shift has been established for oncolytic viruses (OVs) as it was shown that the immune system plays an important role in the specific killing of tumor cells by OVs. OVs have the intrinsic capacity to provide the right signals to trigger anti-tumor immune responses, on the one hand by delivering virus-derived innate signals and on the other hand by inducing immunogenic cell death (ICD), which is accompanied by the release of various damage-associated molecules from infected tumor cells. Here, we determined the ICD-inducing capacity of Talimogene laherparepvec (T-VEC), a herpes simplex virus type 1 based OV, and benchmarked this to other previously described ICD (e.g., doxorubicin) and non-ICD inducing agents (cisplatin). Furthermore, we studied the capability of T-VEC to induce the maturation of human BDCA-1+ myeloid dendritic cells (myDCs). We found that T-VEC treatment exerts direct and indirect anti-tumor effects as it induces tumor cell death that coincides with the release of hallmark mediators of ICD, while simultaneously contributing to the maturation of BDCA-1+ myDCs. These results unequivocally cement OVs in the category of cancer immunotherapy. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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13 pages, 2780 KiB  
Article
β-Catenin-Specific Inhibitor, iCRT14, Promotes BoHV-1 Infection-Induced DNA Damage in Human A549 Lung Adenocarcinoma Cells by Enhancing Viral Protein Expression
by Xiuyan Ding, Weifeng Yuan, Hao Yang, Chang Liu, Shitao Li and Liqian Zhu
Int. J. Mol. Sci. 2022, 23(4), 2328; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23042328 - 19 Feb 2022
Cited by 3 | Viewed by 2118
Abstract
Oncolytic bovine herpesvirus type 1 (BoHV-1) infection induces DNA damage in human lung adenocarcinoma cell line A549. However, the underlying mechanisms are not fully understood. We found that BoHV-1 infection decreased the steady-state protein levels of p53-binding protein 1 (53BP1), which plays a [...] Read more.
Oncolytic bovine herpesvirus type 1 (BoHV-1) infection induces DNA damage in human lung adenocarcinoma cell line A549. However, the underlying mechanisms are not fully understood. We found that BoHV-1 infection decreased the steady-state protein levels of p53-binding protein 1 (53BP1), which plays a central role in dictating DNA damage repair and maintaining genomic stability. Furthermore, BoHV-1 impaired the formation of 53BP1 foci, suggesting that BoHV-1 inhibits 53BP1-mediated DNA damage repair. Interestingly, BoHV-1 infection redistributed intracellular β-catenin, and iCRT14 (5-[[2,5-Dimethyl-1-(3-pyridinyl)-1H-pyrrol-3-yl]methylene]-3-phenyl-2,4-thiazolidinedione), a β-catenin-specific inhibitor, enhanced certain viral protein expression, such as the envelope glycoproteins gC and gD, and enhanced virus infection-induced DNA damage. Therefore, for the first time, we provide evidence showing that BoHV-1 infection disrupts 53BP1-mediated DNA damage repair and suggest β-catenin as a potential host factor restricting both virus replication and DNA damage in A549 cells. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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15 pages, 1524 KiB  
Article
Generation of a Retargeted Oncolytic Herpes Virus Encoding Adenosine Deaminase for Tumor Adenosine Clearance
by Chiara Gentile, Arianna Finizio, Guendalina Froechlich, Anna Morena D’Alise, Gabriella Cotugno, Sara Amiranda, Alfredo Nicosia, Elisa Scarselli, Nicola Zambrano and Emanuele Sasso
Int. J. Mol. Sci. 2021, 22(24), 13521; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413521 - 16 Dec 2021
Cited by 5 | Viewed by 3044
Abstract
Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated [...] Read more.
Background: Oncolytic viruses are immunotherapeutic agents that can be engineered to encode payloads of interest within the tumor microenvironment to enhance therapeutic efficacy. Their therapeutic potential could be limited by many avenues for immune evasion exerted by the tumor. One such is mediated by adenosine, which induces pleiotropic immunosuppression by inhibiting antitumor immune populations as well as activating tolerogenic stimuli. Adenosine is produced starting from the highly immunostimulatory ATP, which is progressively hydrolyzed to ADP and adenosine by CD39 and CD73. Cancer cells express high levels of CD39 and CD73 ectoenzymes, thus converting immunostimulatory purinergic signal of ATP into an immunosuppressive signal. For this reason, CD39, CD73 and adenosine receptors are currently investigated in clinical trials as targets for metabolic cancer immunotherapy. This is of particular relevance in the context of oncovirotherapy, as immunogenic cell death induced by oncolytic viruses causes the secretion of a high amount of ATP which is available to be quickly converted into adenosine. Methods: Here, we took advantage of adenosine deaminase enzyme that naturally converts adenosine into the corresponding inosine derivative, devoid of immunoregulatory function. We encoded ADA into an oncolytic targeted herpes virus redirected to human HER2. An engineered ADA with an ectopic signal peptide was also generated to improve enzyme secretion (ADA-SP). Results: Insertion of the expression cassette was not detrimental for viral yield and cancer cell cytotoxicity. The THV_ADA and THV_ADA-SP successfully mediated the secretion of functional ADA enzyme. In in vitro model of human monocytes THP1, this ability of THV_ADA and THV_ADA-SP resulted in the retrieval of eADO-exposed monocytes replication rate, suggesting the proficiency of the viruses in rescuing the immune function. Conclusions: Encoding ADA into oncolytic viruses revealed promising properties for preclinical exploitation. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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22 pages, 30442 KiB  
Article
Intratumoral Canine Distemper Virus Infection Inhibits Tumor Growth by Modulation of the Tumor Microenvironment in a Murine Xenograft Model of Canine Histiocytic Sarcoma
by Federico Armando, Adnan Fayyad, Stefanie Arms, Yvonne Barthel, Dirk Schaudien, Karl Rohn, Matteo Gambini, Mara Sophie Lombardo, Andreas Beineke, Wolfgang Baumgärtner and Christina Puff
Int. J. Mol. Sci. 2021, 22(7), 3578; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073578 - 30 Mar 2021
Cited by 7 | Viewed by 3171
Abstract
Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication [...] Read more.
Histiocytic sarcomas refer to highly aggressive tumors with a poor prognosis that respond poorly to conventional treatment approaches. Oncolytic viruses, which have gained significant traction as a cancer therapy in recent decades, represent a promising option for treating histiocytic sarcomas through their replication and/or by modulating the tumor microenvironment. The live attenuated canine distemper virus (CDV) vaccine strain Onderstepoort represents an attractive candidate for oncolytic viral therapy. In the present study, oncolytic virotherapy with CDV was used to investigate the impact of this virus infection on tumor cell growth through direct oncolytic effects or by virus-mediated modulation of the tumor microenvironment with special emphasis on angiogenesis, expression of selected MMPs and TIMP-1 and tumor-associated macrophages in a murine xenograft model of canine histiocytic sarcoma. Treatment of mice with xenotransplanted canine histiocytic sarcomas using CDV induced overt retardation in tumor progression accompanied by necrosis of neoplastic cells, increased numbers of intratumoral macrophages, reduced angiogenesis and modulation of the expression of MMPs and TIMP-1. The present data suggest that CDV inhibits tumor growth in a multifactorial way, including direct cell lysis and reduction of angiogenesis and modulation of MMPs and their inhibitor TIMP-1, providing further support for the concept of its role in oncolytic therapies. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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Review

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19 pages, 1241 KiB  
Review
Oncolytic Viruses in the Era of Omics, Computational Technologies, and Modeling: Thesis, Antithesis, and Synthesis
by Laura Menotti and Andrea Vannini
Int. J. Mol. Sci. 2023, 24(24), 17378; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms242417378 - 12 Dec 2023
Viewed by 1053
Abstract
Oncolytic viruses (OVs) are the frontier therapy for refractory cancers, especially in integration with immunomodulation strategies. In cancer immunovirotherapy, the many available “omics” and systems biology technologies generate at a fast pace a challenging huge amount of data, where apparently clashing information mirrors [...] Read more.
Oncolytic viruses (OVs) are the frontier therapy for refractory cancers, especially in integration with immunomodulation strategies. In cancer immunovirotherapy, the many available “omics” and systems biology technologies generate at a fast pace a challenging huge amount of data, where apparently clashing information mirrors the complexity of individual clinical situations and OV used. In this review, we present and discuss how currently big data analysis, on one hand and, on the other, simulation, modeling, and computational technologies, provide invaluable support to interpret and integrate “omic” information and drive novel synthetic biology and personalized OV engineering approaches for effective immunovirotherapy. Altogether, these tools, possibly aided in the future by artificial intelligence as well, will allow for the blending of the information into OV recombinants able to achieve tumor clearance in a patient-tailored way. Various endeavors to the envisioned “synthesis” of turning OVs into personalized theranostic agents are presented. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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25 pages, 31037 KiB  
Review
Molecular MRI-Based Monitoring of Cancer Immunotherapy Treatment Response
by Nikita Vladimirov and Or Perlman
Int. J. Mol. Sci. 2023, 24(4), 3151; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043151 - 05 Feb 2023
Cited by 5 | Viewed by 2792
Abstract
Immunotherapy constitutes a paradigm shift in cancer treatment. Its FDA approval for several indications has yielded improved prognosis for cases where traditional therapy has shown limited efficiency. However, many patients still fail to benefit from this treatment modality, and the exact mechanisms responsible [...] Read more.
Immunotherapy constitutes a paradigm shift in cancer treatment. Its FDA approval for several indications has yielded improved prognosis for cases where traditional therapy has shown limited efficiency. However, many patients still fail to benefit from this treatment modality, and the exact mechanisms responsible for tumor response are unknown. Noninvasive treatment monitoring is crucial for longitudinal tumor characterization and the early detection of non-responders. While various medical imaging techniques can provide a morphological picture of the lesion and its surrounding tissue, a molecular-oriented imaging approach holds the key to unraveling biological effects that occur much earlier in the immunotherapy timeline. Magnetic resonance imaging (MRI) is a highly versatile imaging modality, where the image contrast can be tailored to emphasize a particular biophysical property of interest using advanced engineering of the imaging pipeline. In this review, recent advances in molecular-MRI based cancer immunotherapy monitoring are described. Next, the presentation of the underlying physics, computational, and biological features are complemented by a critical analysis of the results obtained in preclinical and clinical studies. Finally, emerging artificial intelligence (AI)-based strategies to further distill, quantify, and interpret the image-based molecular MRI information are discussed in terms of perspectives for the future. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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9 pages, 1418 KiB  
Review
SARS-CoV-2 as an Oncolytic Virus Following Reactivation of the Immune System: A Review
by Joao P. Bounassar-Filho, Laura Boeckler-Troncoso, Jocelyne Cajigas-Gonzalez and Maria G. Zavala-Cerna
Int. J. Mol. Sci. 2023, 24(3), 2326; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032326 - 24 Jan 2023
Cited by 8 | Viewed by 3347
Abstract
The effects SARS-CoV-2 inflicts on human physiology, especially in patients who developed COVID-19, can range from flu-like symptoms to death, and although many lives have been lost during the pandemic, others have faced the resolution of aggressive neoplasms that once proclaimed a poor [...] Read more.
The effects SARS-CoV-2 inflicts on human physiology, especially in patients who developed COVID-19, can range from flu-like symptoms to death, and although many lives have been lost during the pandemic, others have faced the resolution of aggressive neoplasms that once proclaimed a poor prognosis following traditional treatments. The purpose of this review was to analyze several fortunate case reports and their associated biomolecular pathways to further explore new avenues that might provide oncological treatments in the future of medicine. We included papers that discussed cases in which patients affected by COVID-19 suffered beneficial changes in their cancer status. Multiple mechanisms which elicited a reactivation of the host’s immune system included cross-reactivity with viral antigens and downregulation of neoplastic cells. We were able to identify important cases presenting the resolution/remission of different aggressive neoplasms, for which most of the time, standard-of-care treatments offered little to no prospect towards a cure. The intricacy of the defense mechanisms humans have adopted against cancer cells through the millennia are still not well understood, but SARS-CoV-2 has demonstrated that the same ruinous cytokine storm which has taken so many lives can paradoxically be the answer we have been looking for to recalibrate the immunological system to retarget and vanquish malignancies. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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31 pages, 1670 KiB  
Review
Oncolyic Virotherapy for Prostate Cancer: Lighting a Fire in Winter
by Gongwei Wang, Ying Liu, Shuoru Liu, Yuan Lin and Cheng Hu
Int. J. Mol. Sci. 2022, 23(20), 12647; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012647 - 21 Oct 2022
Cited by 3 | Viewed by 2737
Abstract
As the most common cancer of the genitourinary system, prostate cancer (PCa) is a global men′s health problem whose treatments are an urgent research issue. Treatment options for PCa include active surveillance (AS), surgery, endocrine therapy, chemotherapy, radiation therapy, immunotherapy, etc. However, as [...] Read more.
As the most common cancer of the genitourinary system, prostate cancer (PCa) is a global men′s health problem whose treatments are an urgent research issue. Treatment options for PCa include active surveillance (AS), surgery, endocrine therapy, chemotherapy, radiation therapy, immunotherapy, etc. However, as the cancer progresses, the effectiveness of treatment options gradually decreases, especially in metastatic castration-resistant prostate cancer (mCRPC), for which there are fewer therapeutic options and which have a shorter survival period and worse prognosis. For this reason, oncolytic viral therapy (PV), with its exceptional properties of selective tumor killing, relatively good safety in humans, and potential for transgenic delivery, has attracted increasing attention as a new form of anti-tumor strategy for PCa. There is growing evidence that OV not only kills tumor cells directly by lysis but can also activate anticancer immunity by acting on the tumor microenvironment (TME), thereby preventing tumor growth. In fact, evidence of the efficacy of this strategy has been observed since the late 19th century. However, subsequently, interest waned. The renewed interest in this therapy was due to advances in biotechnological methods and innovations at the end of the 20th century, which was also the beginning of PCa therapy with OV. Moreover, in combination with chemotherapy, radiotherapy, gene therapy or immunotherapy, OV viruses can have a wide range of applications and can provide an effective therapeutic result in the treatment of PCa. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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21 pages, 1443 KiB  
Review
Concepts in Oncolytic Adenovirus Therapy
by Klaus Mantwill, Florian Gerhard Klein, Dongbiao Wang, Sruthi Vasantamadhava Hindupur, Maximilian Ehrenfeld, Per Sonne Holm and Roman Nawroth
Int. J. Mol. Sci. 2021, 22(19), 10522; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910522 - 29 Sep 2021
Cited by 38 | Viewed by 5369
Abstract
Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors [...] Read more.
Oncolytic adenovirus therapy is gaining importance as a novel treatment option for the management of various cancers. Different concepts of modification within the adenovirus vector have been identified that define the mode of action against and the interaction with the tumour. Adenoviral vectors allow for genetic manipulations that restrict tumour specificity and also the expression of specific transgenes in order to support the anti-tumour effect. Additionally, replication of the virus and reinfection of neighbouring tumour cells amplify the therapeutic effect. Another important aspect in oncolytic adenovirus therapy is the virus induced cell death which is a process that activates the immune system against the tumour. This review describes which elements in adenovirus vectors have been identified for modification not only to utilize oncolytic adenovirus vectors into conditionally replicating adenoviruses (CRAds) that allow replication specifically in tumour cells but also to confer specific characteristics to these viruses. These advances in development resulted in clinical trials that are summarized based on the conceptual design. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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Other

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11 pages, 2653 KiB  
Case Report
Intracranial Virotherapy for a Canine Hemangioma
by Pablo Delgado-Bonet, Beatriz Davinia Tomeo-Martín, Blanca Delgado-Bonet, David Sardón-Ruiz, Angel Torrado-Carvajal, Isidro Mateo and Ana Judith Perisé-Barrios
Int. J. Mol. Sci. 2022, 23(19), 11677; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911677 - 02 Oct 2022
Cited by 1 | Viewed by 1843
Abstract
Intracranial hemangiomas are rare neoplastic lesions in dogs that usually appear with life-threatening symptoms. The treatment of choice is tumor resection; however, complete resection is rarely achieved. The patient’s prognosis therefore usually worsens due to tumor progression, and adjuvant treatments are required to [...] Read more.
Intracranial hemangiomas are rare neoplastic lesions in dogs that usually appear with life-threatening symptoms. The treatment of choice is tumor resection; however, complete resection is rarely achieved. The patient’s prognosis therefore usually worsens due to tumor progression, and adjuvant treatments are required to control the disease. Oncolytic viruses are an innovative approach that lyses the tumor cells and induces immune responses. Here, we report the intratumoral inoculation of ICOCAV15 (an oncolytic adenovirus) in a canine intracranial hemangioma, as adjuvant treatment for incomplete tumor resection. The canine patient showed no side effects, and the tumor volume decreased over the 12 months after the treatment, as measured by magnetic resonance imaging using volumetric criteria. When progressive disease was detected at month 18, a new dose of ICOCAV15 was administered. The patient died 31.9 months after the first inoculation of the oncolytic adenovirus. Furthermore, tumor-infiltrated immune cells increased in number after the viral administrations, suggesting tumor microenvironment activation. The increased number of infiltrated immune cells, the long survival time and the absence of side effects suggest that ICOCAV15 could be a safe and effective treatment and should be further explored as a novel therapy for canine hemangiomas. Full article
(This article belongs to the Special Issue Oncolytic Virotherapy 2.0)
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