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Cancers
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Oncolytic Virus Immunotherapy
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Oncolytic Virus Immunotherapy

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

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 80166

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Antonio Marchini

E-Mail Website
Guest Editor
1. German Cancer Research Center, 69120 Heidelberg, Germany
2. Luxembourg Institute of Health, L-1526 Luxembourg, Luxembourg
Interests: oncolytic viruses; rodent protoparvoviruses; combination therapy; immunogenic cell death; virus-host cell interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Carolina S. Ilkow

E-Mail Website
Guest Editor
Affiliation 1: Cancer Therapeutics Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
Affiliation 2: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Interests: immunotherapies for cancer; oncolytic viruses; exosomes; tumor microenvironment
Prof. Alan Melcher

E-Mail Website
Guest Editor
Institute of Cancer Research, London SW3 6JB, UK
Interests: oncolytic viruses; clinical cancer immunotherapy; head and neck cancer; melanoma

Special Issue Information

Dear Colleagues,

Oncolytic viruses (OV) are self-propagating agents that can selectively induce the lysis of cancer cells while sparing normal tissues. OV-mediated cancer cell death is often immunogenic and triggers robust anticancer immune responses and immunoconversion of tumor microenvironments. This makes oncolytic virotherapy a promising new form of immunotherapy and OVs ideal candidates for combination therapy with other anticancer agents, including other immunotherapeutics. There are more than 40 OV from nine different families in clinical development and many more at the preclinical stage. Each OV has its own unique characteristics, its pros and cons. Although herpes simplex virus is currently the lead clinical agent, a real champion among the OVs has not yet emerged, justifying the continuous development and optimization of these agents. In this Special Issue of Cancers, we aim to compile reviews that summarize the state-of-the-art and give a comprehensive overview of the OV arena with a particular focus on new trends, directions, challenges, and opportunities.

Dr. Antonio Marchini
Dr. Carolina S. Ilkow
Prof. Alan Melcher
Guest Editors

Manuscript Submission Information

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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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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 viruses
  • immunotherapy
  • combination therapy
  • tumor microenvironment
  • immunogenic cell death
  • new anticancer strategies

Published Papers (17 papers)

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Editorial

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4 pages, 192 KiB  
Editorial
Oncolytic Virus Immunotherapy
by Antonio Marchini, Carolina S. Ilkow and Alan Melcher
Cancers 2021, 13(15), 3672; https://doi.org/10.3390/cancers13153672 - 22 Jul 2021
Cited by 5 | Viewed by 2023
Abstract
Oncolytic viruses (OVs) were originally developed as direct cytotoxic agents but have been increasingly recognised as a form of immunotherapy [...] Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)

Review

Jump to: Editorial

31 pages, 4875 KiB  
Review
Combining Oncolytic Viruses and Small Molecule Therapeutics: Mutual Benefits
by Bart Spiesschaert, Katharina Angerer, John Park and Guido Wollmann
Cancers 2021, 13(14), 3386; https://doi.org/10.3390/cancers13143386 - 6 Jul 2021
Cited by 11 | Viewed by 3823
Abstract
The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors [...] Read more.
The focus of treating cancer with oncolytic viruses (OVs) has increasingly shifted towards achieving efficacy through the induction and augmentation of an antitumor immune response. However, innate antiviral responses can limit the activity of many OVs within the tumor and several immunosuppressive factors can hamper any subsequent antitumor immune responses. In recent decades, numerous small molecule compounds that either inhibit the immunosuppressive features of tumor cells or antagonize antiviral immunity have been developed and tested for. Here we comprehensively review small molecule compounds that can achieve therapeutic synergy with OVs. We also elaborate on the mechanisms by which these treatments elicit anti-tumor effects as monotherapies and how these complement OV treatment. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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31 pages, 1928 KiB  
Review
Expanding the Spectrum of Pancreatic Cancers Responsive to Vesicular Stomatitis Virus-Based Oncolytic Virotherapy: Challenges and Solutions
by Molly C. Holbrook, Dakota W. Goad and Valery Z. Grdzelishvili
Cancers 2021, 13(5), 1171; https://doi.org/10.3390/cancers13051171 - 9 Mar 2021
Cited by 10 | Viewed by 4687
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with poor prognosis and a dismal survival rate, expected to become the second leading cause of cancer-related deaths in the United States. Oncolytic virus (OV) is an anticancer approach that utilizes replication-competent viruses to preferentially infect and kill tumor cells. Vesicular stomatitis virus (VSV), one such OV, is already in several phase I clinical trials against different malignancies. VSV-based recombinant viruses are effective OVs against a majority of tested PDAC cell lines. However, some PDAC cell lines are resistant to VSV. Upregulated type I IFN signaling and constitutive expression of a subset of interferon-simulated genes (ISGs) play a major role in such resistance, while other mechanisms, such as inefficient viral attachment and resistance to VSV-mediated apoptosis, also play a role in some PDACs. Several alternative approaches have been shown to break the resistance of PDACs to VSV without compromising VSV oncoselectivity, including (i) combinations of VSV with JAK1/2 inhibitors (such as ruxolitinib); (ii) triple combinations of VSV with ruxolitinib and polycations improving both VSV replication and attachment; (iii) combinations of VSV with chemotherapeutic drugs (such as paclitaxel) arresting cells in the G2/M phase; (iv) arming VSV with p53 transgenes; (v) directed evolution approach producing more effective OVs. The latter study demonstrated impressive long-term genomic stability of complex VSV recombinants encoding large transgenes, supporting further clinical development of VSV as safe therapeutics for PDAC. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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14 pages, 798 KiB  
Review
Parking CAR T Cells in Tumours: Oncolytic Viruses as Valets or Vandals?
by Laura Evgin and Richard G. Vile
Cancers 2021, 13(5), 1106; https://doi.org/10.3390/cancers13051106 - 5 Mar 2021
Cited by 20 | Viewed by 3957
Abstract
Oncolytic viruses (OVs) and adoptive T cell therapy (ACT) each possess direct tumour cytolytic capabilities, and their combination potentially seems like a match made in heaven to complement the strengths and weakness of each modality. While providing strong innate immune stimulation that can [...] Read more.
Oncolytic viruses (OVs) and adoptive T cell therapy (ACT) each possess direct tumour cytolytic capabilities, and their combination potentially seems like a match made in heaven to complement the strengths and weakness of each modality. While providing strong innate immune stimulation that can mobilize adaptive responses, the magnitude of anti-tumour T cell priming induced by OVs is often modest. Chimeric antigen receptor (CAR) modified T cells bypass conventional T cell education through introduction of a synthetic receptor; however, realization of their full therapeutic properties can be stunted by the heavily immune-suppressive nature of the tumour microenvironment (TME). Oncolytic viruses have thus been seen as a natural ally to overcome immunosuppressive mechanisms in the TME which limit CAR T cell infiltration and functionality. Engineering has further endowed viruses with the ability to express transgenes in situ to relieve T cell tumour-intrinsic resistance mechanisms and decorate the tumour with antigen to overcome antigen heterogeneity or loss. Despite this helpful remodeling of the tumour microenvironment, it has simultaneously become clear that not all virus induced effects are favourable for CAR T, begging the question whether viruses act as valets ushering CAR T into their active site, or vandals which cause chaos leading to both tumour and T cell death. Herein, we summarize recent studies combining these two therapeutic modalities and seek to place them within the broader context of viral T cell immunology which will help to overcome the current limitations of effective CAR T therapy to make the most of combinatorial strategies. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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19 pages, 1631 KiB  
Review
Oncolytic Virotherapy: The Cancer Cell Side
by Marcelo Ehrlich and Eran Bacharach
Cancers 2021, 13(5), 939; https://doi.org/10.3390/cancers13050939 - 24 Feb 2021
Cited by 6 | Viewed by 3388
Abstract
Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure [...] Read more.
Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the immunostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced anabolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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14 pages, 983 KiB  
Review
Tackling HLA Deficiencies Head on with Oncolytic Viruses
by Kerry Fisher, Ahmet Hazini and Leonard W. Seymour
Cancers 2021, 13(4), 719; https://doi.org/10.3390/cancers13040719 - 10 Feb 2021
Cited by 5 | Viewed by 2273
Abstract
Dysregulation of HLA (human leukocyte antigen) function is increasingly recognized as a common escape mechanism for cancers subject to the pressures exerted by immunosurveillance or immunotherapeutic interventions. Oncolytic viruses have the potential to counter this resistance by upregulating HLA expression or encouraging an [...] Read more.
Dysregulation of HLA (human leukocyte antigen) function is increasingly recognized as a common escape mechanism for cancers subject to the pressures exerted by immunosurveillance or immunotherapeutic interventions. Oncolytic viruses have the potential to counter this resistance by upregulating HLA expression or encouraging an HLA-independent immunological responses. However, to achieve the best therapeutic outcomes, a prospective understanding of the HLA phenotype of cancer patients is required to match them to the characteristics of different oncolytic strategies. Here, we consider the spectrum of immune competence observed in clinical disease and discuss how it can be best addressed using this novel and powerful treatment approach. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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22 pages, 1870 KiB  
Review
Personalizing Oncolytic Virotherapy for Glioblastoma: In Search of Biomarkers for Response
by Eftychia Stavrakaki, Clemens M. F. Dirven and Martine L. M. Lamfers
Cancers 2021, 13(4), 614; https://doi.org/10.3390/cancers13040614 - 4 Feb 2021
Cited by 24 | Viewed by 4472
Abstract
Oncolytic virus (OV) treatment may offer a new treatment option for the aggressive brain tumor glioblastoma. Clinical trials testing oncolytic viruses in this patient group have shown promising results, with patients achieving impressive long-term clinical responses. However, the number of responders to each [...] Read more.
Oncolytic virus (OV) treatment may offer a new treatment option for the aggressive brain tumor glioblastoma. Clinical trials testing oncolytic viruses in this patient group have shown promising results, with patients achieving impressive long-term clinical responses. However, the number of responders to each OV remains low. This is thought to arise from the large heterogeneity of these tumors, both in terms of molecular make-up and their immune-suppressive microenvironment, leading to variability in responses. An approach that may improve response rates is the personalized utilization of oncolytic viruses against Glioblastoma (GBM), based on specific tumor- or patient-related characteristics. In this review, we discuss potential biomarkers for response to different OVs as well as emerging ex vivo assays that in the future may enable selection of optimal OV for a specific patient and design of stratified clinical OV trials for GBM. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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28 pages, 958 KiB  
Review
Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements
by Ke-Tao Jin, Wen-Lin Du, Yu-Yao Liu, Huan-Rong Lan, Jing-Xing Si and Xiao-Zhou Mou
Cancers 2021, 13(4), 588; https://doi.org/10.3390/cancers13040588 - 3 Feb 2021
Cited by 18 | Viewed by 3910
Abstract
Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, [...] Read more.
Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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18 pages, 1589 KiB  
Review
Measles Virus as an Oncolytic Immunotherapy
by Christine E. Engeland and Guy Ungerechts
Cancers 2021, 13(3), 544; https://doi.org/10.3390/cancers13030544 - 1 Feb 2021
Cited by 48 | Viewed by 6875
Abstract
Measles virus (MeV) preferentially replicates in malignant cells, leading to tumor lysis and priming of antitumor immunity. Live attenuated MeV vaccine strains are therefore under investigation as cancer therapeutics. The versatile MeV reverse genetics systems allows for engineering of advanced targeted, armed, and [...] Read more.
Measles virus (MeV) preferentially replicates in malignant cells, leading to tumor lysis and priming of antitumor immunity. Live attenuated MeV vaccine strains are therefore under investigation as cancer therapeutics. The versatile MeV reverse genetics systems allows for engineering of advanced targeted, armed, and shielded oncolytic viral vectors. Therapeutic efficacy can further be enhanced by combination treatments. An emerging focus in this regard is combination immunotherapy, especially with immune checkpoint blockade. Despite challenges arising from antiviral immunity, availability of preclinical models, and GMP production, early clinical trials have demonstrated safety of oncolytic MeV and yielded promising efficacy data. Future clinical trials with engineered viruses, rational combination regimens, and comprehensive translational research programs will realize the potential of oncolytic immunotherapy. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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15 pages, 1587 KiB  
Review
Parvovirus-Based Combinatorial Immunotherapy: A Reinforced Therapeutic Strategy against Poor-Prognosis Solid Cancers
by Assia Angelova, Tiago Ferreira, Clemens Bretscher, Jean Rommelaere and Antonio Marchini
Cancers 2021, 13(2), 342; https://doi.org/10.3390/cancers13020342 - 19 Jan 2021
Cited by 16 | Viewed by 3547
Abstract
Resistance to anticancer treatments poses continuing challenges to oncology researchers and clinicians. The underlying mechanisms are complex and multifactorial. However, the immunologically “cold” tumor microenvironment (TME) has recently emerged as one of the critical players in cancer progression and therapeutic resistance. Therefore, TME [...] Read more.
Resistance to anticancer treatments poses continuing challenges to oncology researchers and clinicians. The underlying mechanisms are complex and multifactorial. However, the immunologically “cold” tumor microenvironment (TME) has recently emerged as one of the critical players in cancer progression and therapeutic resistance. Therefore, TME modulation through induction of an immunological switch towards inflammation (“warming up”) is among the leading approaches in modern oncology. Oncolytic viruses (OVs) are seen today not merely as tumor cell-killing (oncolytic) agents, but also as cancer therapeutics with multimodal antitumor action. Due to their intrinsic or engineered capacity for overcoming immune escape mechanisms, warming up the TME and promoting antitumor immune responses, OVs hold the potential for creating a proinflammatory background, which may in turn facilitate the action of other (immunomodulating) drugs. The latter provides the basis for the development of OV-based immunostimulatory anticancer combinations. This review deals with the smallest among all OVs, the H-1 parvovirus (H-1PV), and focuses on H-1PV-based combinatorial approaches, whose efficiency has been proven in preclinical and/or clinical settings. Special focus is given to cancer types with the most devastating impact on life expectancy that urgently call for novel therapies. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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22 pages, 5325 KiB  
Review
Immunotherapeutic Efficacy of Retargeted oHSVs Designed for Propagation in an Ad Hoc Cell Line
by Andrea Vannini, Valerio Leoni, Mara Sanapo, Tatiana Gianni, Giorgia Giordani, Valentina Gatta, Catia Barboni, Anna Zaghini and Gabriella Campadelli-Fiume
Cancers 2021, 13(2), 266; https://doi.org/10.3390/cancers13020266 - 12 Jan 2021
Cited by 7 | Viewed by 2624
Abstract
Our laboratory has pursued the generation of cancer-specific oncolytic herpes simplex viruses (oHSVs) which ensure high efficacy while maintaining a high safety profile. Their blueprint included retargeting to a Tumor-Associated Antigen, e.g., HER2, coupled to detargeting from natural receptors to avoid off-target and [...] Read more.
Our laboratory has pursued the generation of cancer-specific oncolytic herpes simplex viruses (oHSVs) which ensure high efficacy while maintaining a high safety profile. Their blueprint included retargeting to a Tumor-Associated Antigen, e.g., HER2, coupled to detargeting from natural receptors to avoid off-target and off-tumor infections and preservation of the full complement of unmodified viral genes. These oHSVs are “fully virulent in their target cancer cells”. The 3rd generation retargeted oHSVs carry two distinct retargeting moieties, which enable infection of a producer cell line and of the target cancer cells, respectively. They can be propagated in an ad hoc Vero cell derivative at about tenfold higher yields than 1st generation recombinants, and more effectively replicate in human cancer cell lines. The R-335 and R-337 prototypes were armed with murine IL-12. Intratumorally-administered R-337 conferred almost complete protection from LLC-1-HER2 primary tumors, unleashed the tumor microenvironment immunosuppression, synergized with the checkpoint blockade and conferred long-term vaccination against distant challenge tumors. In summary, the problem intrinsic to the propagation of retargeted oHSVs—which strictly require cells positive for targeted receptors—was solved in 3rd generation viruses. They are effective as immunotherapeutic agents against primary tumors and as antigen-agnostic vaccines. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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15 pages, 1019 KiB  
Review
Newcastle Disease Virus at the Forefront of Cancer Immunotherapy
by Bharat Burman, Giulio Pesci and Dmitriy Zamarin
Cancers 2020, 12(12), 3552; https://doi.org/10.3390/cancers12123552 - 28 Nov 2020
Cited by 52 | Viewed by 8284
Abstract
Preclinical and clinical studies dating back to the 1950s have demonstrated that Newcastle disease virus (NDV) has oncolytic properties and can potently stimulate antitumor immune responses. NDV selectively infects, replicates within, and lyses cancer cells by exploiting defective antiviral defenses in cancer cells. [...] Read more.
Preclinical and clinical studies dating back to the 1950s have demonstrated that Newcastle disease virus (NDV) has oncolytic properties and can potently stimulate antitumor immune responses. NDV selectively infects, replicates within, and lyses cancer cells by exploiting defective antiviral defenses in cancer cells. Inflammation within the tumor microenvironment in response to NDV leads to the recruitment of innate and adaptive immune effector cells, presentation of tumor antigens, and induction of immune checkpoints. In animal models, intratumoral injection of NDV results in T cell infiltration of both local and distant non-injected tumors, demonstrating the potential of NDV to activate systemic adaptive antitumor immunity. The combination of intratumoral NDV with systemic immune checkpoint blockade leads to regression of both injected and distant tumors, an effect further potentiated by introduction of immunomodulatory transgenes into the viral genome. Clinical trials with naturally occurring NDV administered intravenously demonstrated durable responses across numerous cancer types. Based on these studies, further exploration of NDV is warranted, and clinical studies using recombinant NDV in combination with immune checkpoint blockade have been initiated. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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16 pages, 486 KiB  
Review
HSV-1 Oncolytic Viruses from Bench to Bedside: An Overview of Current Clinical Trials
by Marilin S. Koch, Sean E. Lawler and E. Antonio Chiocca
Cancers 2020, 12(12), 3514; https://doi.org/10.3390/cancers12123514 - 26 Nov 2020
Cited by 38 | Viewed by 4365
Abstract
Herpes simplex virus 1 (HSV-1) provides a genetic chassis for several oncolytic viruses (OVs) currently in clinical trials. Oncolytic HSV1 (oHSV) have been engineered to reduce neurovirulence and enhance anti-tumor lytic activity and immunogenicity to make them attractive candidates in a range of [...] Read more.
Herpes simplex virus 1 (HSV-1) provides a genetic chassis for several oncolytic viruses (OVs) currently in clinical trials. Oncolytic HSV1 (oHSV) have been engineered to reduce neurovirulence and enhance anti-tumor lytic activity and immunogenicity to make them attractive candidates in a range of oncology indications. Successful clinical data resulted in the FDA-approval of the oHSV talimogene laherparepvec (T-Vec) in 2015, and several other variants are currently undergoing clinical assessment and may expand the landscape of future oncologic therapy options. This review offers a detailed overview of the latest results from clinical trials as well as an outlook on newly developed HSV-1 oncolytic variants with improved tumor selectivity, replication, and immunostimulatory capacity and related clinical studies. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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23 pages, 458 KiB  
Review
Oncolytic Adenovirus in Cancer Immunotherapy
by Malin Peter and Florian Kühnel
Cancers 2020, 12(11), 3354; https://doi.org/10.3390/cancers12113354 - 13 Nov 2020
Cited by 28 | Viewed by 6644
Abstract
Tumor-selective replicating “oncolytic” viruses are novel and promising tools for immunotherapy of cancer. However, despite their first success in clinical trials, previous experience suggests that currently used oncolytic virus monotherapies will not be effective enough to achieve complete tumor responses and long-term cure [...] Read more.
Tumor-selective replicating “oncolytic” viruses are novel and promising tools for immunotherapy of cancer. However, despite their first success in clinical trials, previous experience suggests that currently used oncolytic virus monotherapies will not be effective enough to achieve complete tumor responses and long-term cure in a broad spectrum of cancers. Nevertheless, there are reasonable arguments that suggest advanced oncolytic viruses will play an essential role as enablers of multi-stage immunotherapies including established systemic immunotherapies. Oncolytic adenoviruses (oAds) display several features to meet this therapeutic need. oAds potently lyse infected tumor cells and induce a strong immunogenic cell death associated with tumor inflammation and induction of antitumor immune responses. Furthermore, established and versatile platforms of oAds exist, which are well suited for the incorporation of heterologous genes to optimally exploit and amplify the immunostimulatory effect of viral oncolysis. A considerable spectrum of functional genes has already been integrated in oAds to optimize particular aspects of immune stimulation including antigen presentation, T cell priming, engagement of additional effector functions, and interference with immunosuppression. These advanced concepts have the potential to play a promising future role as enablers of multi-stage immunotherapies involving adoptive cell transfer and systemic immunotherapies. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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24 pages, 2542 KiB  
Review
Hitting the Target but Missing the Point: Recent Progress towards Adenovirus-Based Precision Virotherapies
by Tabitha G. Cunliffe, Emily A. Bates and Alan L. Parker
Cancers 2020, 12(11), 3327; https://doi.org/10.3390/cancers12113327 - 11 Nov 2020
Cited by 17 | Viewed by 5464
Abstract
More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for [...] Read more.
More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, although immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus, have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergise with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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26 pages, 1201 KiB  
Review
Past, Present and Future of Oncolytic Reovirus
by Louise Müller, Robert Berkeley, Tyler Barr, Elizabeth Ilett and Fiona Errington-Mais
Cancers 2020, 12(11), 3219; https://doi.org/10.3390/cancers12113219 - 31 Oct 2020
Cited by 60 | Viewed by 5350
Abstract
Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct [...] Read more.
Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a “one size fits all” approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations. This article will provide an unbiased review of oncolytic reovirus (clinically formulated as pelareorep), including the molecular and cellular requirements for reovirus oncolysis and anti-tumour immunity, reports of pre-clinical efficacy and its overall clinical trajectory. Moreover, as it is now abundantly clear that the true potential of all OVs, including reovirus, will only be reached upon the development of synergistic combination strategies, reovirus combination therapeutics will be discussed, including the limitations and challenges that remain to harness the full potential of this promising therapeutic agent. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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20 pages, 1788 KiB  
Review
From Conventional Therapies to Immunotherapy: Melanoma Treatment in Review
by Lukasz Kuryk, Laura Bertinato, Monika Staniszewska, Katarzyna Pancer, Magdalena Wieczorek, Stefano Salmaso, Paolo Caliceti and Mariangela Garofalo
Cancers 2020, 12(10), 3057; https://doi.org/10.3390/cancers12103057 - 20 Oct 2020
Cited by 48 | Viewed by 6322
Abstract
In this review, we discuss the use of oncolytic viruses and checkpoint inhibitors in cancer immunotherapy in melanoma, with a particular focus on combinatory therapies. Oncolytic viruses are promising and novel anti-cancer agents, currently under investigation in many clinical trials both as monotherapy [...] Read more.
In this review, we discuss the use of oncolytic viruses and checkpoint inhibitors in cancer immunotherapy in melanoma, with a particular focus on combinatory therapies. Oncolytic viruses are promising and novel anti-cancer agents, currently under investigation in many clinical trials both as monotherapy and in combination with other therapeutics. They have shown the ability to exhibit synergistic anticancer activity with checkpoint inhibitors, chemotherapy, radiotherapy. A coupling between oncolytic viruses and checkpoint inhibitors is a well-accepted strategy for future cancer therapies. However, eradicating advanced cancers and tailoring the immune response for complete tumor clearance is an ongoing problem. Despite current advances in cancer research, monotherapy has shown limited efficacy against solid tumors. Therefore, current improvements in virus targeting, genetic modification, enhanced immunogenicity, improved oncolytic properties and combination strategies have a potential to widen the applications of immuno-oncology (IO) in cancer treatment. Here, we summarize the strategy of combinatory therapy with an oncolytic vector to combat melanoma and highlight the need to optimize current practices and improve clinical outcomes. Full article
(This article belongs to the Special Issue Oncolytic Virus Immunotherapy)
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