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16 pages, 2719 KiB

Open AccessArticle

Generation of an Oncolytic Herpes Simplex Viral Vector Completely Retargeted to the GDNF Receptor GFRα1 for Specific Infection of Breast Cancer Cells

by Bonnie L. Hall, Daniela Leronni, Yoshitaka Miyagawa, William F. Goins, Joseph C. Glorioso and Justus B. Cohen

Int. J. Mol. Sci. 2020, 21(22), 8815; https://doi.org/10.3390/ijms21228815 - 21 Nov 2020

Cited by 10 | Viewed by 3021

Abstract

Oncolytic herpes simplex viruses (oHSV) are under development for the treatment of a variety of human cancers, including breast cancer, a leading cause of cancer mortality among women worldwide. Here we report the design of a fully retargeted oHSV for preferential infection of [...] Read more.

Oncolytic herpes simplex viruses (oHSV) are under development for the treatment of a variety of human cancers, including breast cancer, a leading cause of cancer mortality among women worldwide. Here we report the design of a fully retargeted oHSV for preferential infection of breast cancer cells through virus recognition of GFRα1, the cellular receptor for glial cell-derived neurotrophic factor (GDNF). GFRα1 displays a limited expression profile in normal adult tissue, but is upregulated in a subset of breast cancers. We generated a recombinant HSV expressing a completely retargeted glycoprotein D (gD), the viral attachment/entry protein, that incorporates pre-pro-GDNF in place of the signal peptide and HVEM binding domain of gD and contains a deletion of amino acid 38 to eliminate nectin-1 binding. We show that GFRα1 is necessary and sufficient for infection by the purified recombinant virus. Moreover, this virus enters and spreads in GFRα1-positive breast cancer cells in vitro and caused tumor regression upon intratumoral injection in vivo. Given the heterogeneity observed between and within individual breast cancers at the molecular level, these results expand our ability to deliver oHSV to specific tumors and suggest opportunities to enhance drug or viral treatments aimed at other receptors. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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19 pages, 8119 KiB

Open AccessArticle

Assessing and Overcoming Resistance Phenomena against a Genetically Modified Vaccinia Virus in Selected Cancer Cell Lines

by Susanne Berchtold, Julia Beil, Christian Raff, Irina Smirnow, Martina Schell, Janina D’Alvise, Silvia Gross and Ulrich M. Lauer

Int. J. Mol. Sci. 2020, 21(20), 7618; https://doi.org/10.3390/ijms21207618 - 15 Oct 2020

Cited by 7 | Viewed by 2303

Abstract

Genetically modified vaccinia viruses (VACVs) have been shown to possess profound oncolytic capabilities. However, tumor cell resistance to VACVs may endanger broad clinical success. Using cell mass assays, viral replication studies, and fluorescence microscopy, we investigated primary resistance phenomena of cell lines of [...] Read more.

Genetically modified vaccinia viruses (VACVs) have been shown to possess profound oncolytic capabilities. However, tumor cell resistance to VACVs may endanger broad clinical success. Using cell mass assays, viral replication studies, and fluorescence microscopy, we investigated primary resistance phenomena of cell lines of the NCI-60 tumor cell panel to GLV-1h94, a derivative of the Lister strain of VACV, which encodes the enzyme super cytosine deaminase (SCD) that converts the prodrug 5-fluorocytosine (5-FC) into the chemotherapeutic compound 5-fluorouracil (5-FU). After treatment with GLV-1h94 alone, only half of the cell lines were defined as highly susceptible to GLV-1h94-induced oncolysis. When adding 5-FC, 85% of the cell lines became highly susceptible to combinatorial treatment; none of the tested tumor cell lines exhibited a “high-grade resistance” pattern. Detailed investigation of the SCD prodrug system suggested that the cytotoxic effect of converted 5-FU is directed either against the cells or against the virus particles, depending on the balance between cell line-specific susceptibility to GLV-1h94-induced oncolysis and 5-FU sensitivity. The data provided by this work underline that cellular resistance against VACV-based virotherapy can be overcome by virus-encoded prodrug systems. Phase I/II clinical trials are recommended to further elucidate the enormous potential of this combination therapy. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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15 pages, 2351 KiB

Open AccessArticle

Pharmacological Inhibition of WEE1 Potentiates the Antitumoral Effect of the dl922-947 Oncolytic Virus in Malignant Mesothelioma Cell Lines

by Carmelina Antonella Iannuzzi, Paola Indovina, Iris Maria Forte, Sarah Di Somma, Anna Maria Malfitano, Martina Bruno, Giuseppe Portella, Francesca Pentimalli and Antonio Giordano

Int. J. Mol. Sci. 2020, 21(19), 7333; https://doi.org/10.3390/ijms21197333 - 4 Oct 2020

Cited by 4 | Viewed by 3559

Abstract

Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host [...] Read more.

Malignant mesothelioma (MM) is a very aggressive asbestos-related cancer, for which no therapy proves to be effective. We have recently shown that the oncolytic adenovirus dl922-947 had antitumor effects in MM cell lines and murine xenografts. Previous studies demonstrated that dl922-947-induced host cell cycle checkpoint deregulation and consequent DNA lesions associated with the virus efficacy. However, the cellular DNA damage response (DDR) can counteract this virus action. Therefore, we assessed whether AZD1775, an inhibitor of the G2/M DNA damage checkpoint kinase WEE1, could enhance MM cell sensitivity to dl922-947. Through cell viability assays, we found that AZD1775 synergized with dl922-947 selectively in MM cell lines and increased dl922-947-induced cell death, which showed hallmarks of apoptosis (annexinV-positivity, caspase-dependency, BCL-XL decrease, chromatin condensation). Predictably, dl922-947 and/or AZD1775 activated the DDR, as indicated by increased levels of three main DDR players: phosphorylated histone H2AX (γ-H2AX), phospho-replication protein A (RPA)32, phospho-checkpoint kinase 1 (CHK1). Dl922-947 also increased inactive Tyr-15-phosphorylated cyclin-dependent kinase 1 (CDK1), a key WEE1 substrate, which is indicative of G2/M checkpoint activation. This increase in phospho-CDK1 was effectively suppressed by AZD1775, thus suggesting that this compound could, indeed, abrogate the dl922-947-induced DNA damage checkpoint in MM cells. Overall, our data suggest that the dl922-947-AZD1775 combination could be a feasible strategy against MM. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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14 pages, 3054 KiB

Open AccessArticle

Vitamin D as a Primer for Oncolytic Viral Therapy in Colon Cancer Models

by Sang-In Kim, Shyambabu Chaurasiya, Anthony K. Park, Seonah Kang, Jianming Lu, Yanghee Woo, Hongwei Holly Yin, Zhirong Yin, Yuman Fong and Susanne G. Warner

Int. J. Mol. Sci. 2020, 21(19), 7326; https://doi.org/10.3390/ijms21197326 - 3 Oct 2020

Cited by 4 | Viewed by 2705

Abstract

Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D [...] Read more.

Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for colon cancer. While vitamin D (VD) has historically been viewed as anti-viral, our in vitro investigations using human colon cancer cell lines showed that VD does not directly inhibit replication of recombinant chimeric poxvirus CF33. VD did restrict growth in HT29 but not HCT116 human colon cancer cells. In vivo investigations using HCT116 and HT29 xenograft models of colon cancer demonstrated that a VD analogue, calcipotriol, was additive with CF33-based viral therapy in VD-responsive HT29 but not in HCT116 tumors. Analyses of RNA-sequencing and gene expression data demonstrated a downregulation in the Jak-STAT signaling pathway with the addition of VD to viral therapy in HT29 models suggesting that the anti-inflammatory properties of VD may enhance the effects of viral therapy in some models. In conclusion, VD may prime oncolytic viral therapy in certain colon cancers. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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Review

Jump to: Research

13 pages, 1842 KiB

Open AccessReview

Real-Time Fluorescence Image-Guided Oncolytic Virotherapy for Precise Cancer Treatment

by Shuya Yano, Hiroshi Tazawa, Hiroyuki Kishimoto, Shunsuke Kagawa, Toshiyoshi Fujiwara and Robert M. Hoffman

Int. J. Mol. Sci. 2021, 22(2), 879; https://doi.org/10.3390/ijms22020879 - 17 Jan 2021

Cited by 8 | Viewed by 4798

Abstract

Oncolytic virotherapy is one of the most promising, emerging cancer therapeutics. We generated three types of telomerase-specific replication-competent oncolytic adenovirus: OBP-301; a green fluorescent protein (GFP)-expressing adenovirus, OBP-401; and Killer-Red-armed OBP-301. These oncolytic adenoviruses are driven by the human telomerase reverse transcriptase (hTERT) [...] Read more.

Oncolytic virotherapy is one of the most promising, emerging cancer therapeutics. We generated three types of telomerase-specific replication-competent oncolytic adenovirus: OBP-301; a green fluorescent protein (GFP)-expressing adenovirus, OBP-401; and Killer-Red-armed OBP-301. These oncolytic adenoviruses are driven by the human telomerase reverse transcriptase (hTERT) promoter; therefore, they conditionally replicate preferentially in cancer cells. Fluorescence imaging enables visualization of invasion and metastasis in vivo at the subcellular level; including molecular dynamics of cancer cells, resulting in greater precision therapy. In the present review, we focused on fluorescence imaging applications to develop precision targeting for oncolytic virotherapy. Cell-cycle imaging with the fluorescence ubiquitination cell cycle indicator (FUCCI) demonstrated that combination therapy of an oncolytic adenovirus and a cytotoxic agent could precisely target quiescent, chemoresistant cancer stem cells (CSCs) based on decoying the cancer cells to cycle to S-phase by viral treatment, thereby rendering them chemosensitive. Non-invasive fluorescence imaging demonstrated that complete tumor resection with a precise margin, preservation of function, and prevention of distant metastasis, was achieved with fluorescence-guided surgery (FGS) with a GFP-reporter adenovirus. A combination of fluorescence imaging and laser ablation using a KillerRed-protein reporter adenovirus resulted in effective photodynamic cancer therapy (PDT). Thus, imaging technology and the designer oncolytic adenoviruses may have clinical potential for precise cancer targeting by indicating the optimal time for administering therapeutic agents; accurate surgical guidance for complete resection of tumors; and precise targeted cancer-specific photosensitization. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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24 pages, 406 KiB

Open AccessReview

Oncolytic Viruses and Immune Checkpoint Inhibitors: Preclinical Developments to Clinical Trials

by June Kyu Hwang, JinWoo Hong and Chae-Ok Yun

Int. J. Mol. Sci. 2020, 21(22), 8627; https://doi.org/10.3390/ijms21228627 - 16 Nov 2020

Cited by 56 | Viewed by 5128

Abstract

Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has [...] Read more.

Immuno-oncology (IO) has been an active area of oncology research. Following US FDA approval of the first immune checkpoint inhibitor (ICI), ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody), in 2011, and of the first oncolytic virus, Imlygic (talimogene laherparepvec), in 2015, there has been renewed interest in IO. In the past decade, ICIs have changed the treatment paradigm for many cancers by enabling better therapeutic control, resuming immune surveillance, suppressing tumor immunosuppression, and restoring antitumor immune function. However, ICI therapies are effective only in a small subset of patients and show limited therapeutic potential due to their inability to demonstrate efficacy in ‘cold’ or unresponsive tumor microenvironments (TMEs). Relatedly, oncolytic viruses (OVs) have been shown to induce antitumor immune responses, augment the efficacy of existing cancer treatments, and reform unresponsive TME to turn ‘cold’ tumors ‘hot,’ increasing their susceptibility to checkpoint blockade immunotherapies. For this reason, OVs serve as ideal complements to ICIs, and multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy. This review will discuss the merits and limitations of OVs and ICIs as monotherapy then progress onto the preclinical rationale and the results of clinical trials of key combination therapies. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

26 pages, 1723 KiB

Open AccessReview

Herpes Simplex Virus Oncolytic Immunovirotherapy: The Blossoming Branch of Multimodal Therapy

by Laura Menotti and Elisa Avitabile

Int. J. Mol. Sci. 2020, 21(21), 8310; https://doi.org/10.3390/ijms21218310 - 5 Nov 2020

Cited by 29 | Viewed by 5146

Abstract

Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their [...] Read more.

Oncolytic viruses are smart therapeutics against cancer due to their potential to replicate and produce the needed therapeutic dose in the tumor, and to their ability to self-exhaust upon tumor clearance. Oncolytic virotherapy strategies based on the herpes simplex virus are reaching their thirties, and a wide variety of approaches has been envisioned and tested in many different models, and on a range of tumor targets. This huge effort has culminated in the primacy of an oncolytic HSV (oHSV) being the first oncolytic virus to be approved by the FDA and EMA for clinical use, for the treatment of advanced melanoma. The path has just been opened; many more cancer types with poor prognosis await effective and innovative therapies, and oHSVs could provide a promising solution, especially as combination therapies and immunovirotherapies. In this review, we analyze the most recent advances in this field, and try to envision the future ahead of oHSVs. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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16 pages, 680 KiB

Open AccessReview

Combination Immunotherapy Using Oncolytic Virus for the Treatment of Advanced Solid Tumors

by Chang-Myung Oh, Hong Jae Chon and Chan Kim

Int. J. Mol. Sci. 2020, 21(20), 7743; https://doi.org/10.3390/ijms21207743 - 19 Oct 2020

Cited by 39 | Viewed by 5080

Abstract

Oncolytic virus (OV) is a new therapeutic strategy for cancer treatment. OVs can selectively infect and destroy cancer cells, and therefore act as an in situ cancer vaccine by releasing tumor-specific antigens. Moreover, they can remodel the tumor microenvironment toward a T cell-inflamed [...] Read more.

Oncolytic virus (OV) is a new therapeutic strategy for cancer treatment. OVs can selectively infect and destroy cancer cells, and therefore act as an in situ cancer vaccine by releasing tumor-specific antigens. Moreover, they can remodel the tumor microenvironment toward a T cell-inflamed phenotype by stimulating widespread host immune responses against the tumor. Recent evidence suggests several possible applications of OVs against cancer, especially in combination with immune checkpoint inhibitors. In this review, we describe the molecular mechanisms of oncolytic virotherapy and OV-induced immune responses, provide a brief summary of recent preclinical and clinical updates on this rapidly evolving field, and discuss a combinational strategy that is able to overcome the limitations of OV-based monotherapy. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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30 pages, 833 KiB

Open AccessReview

Oncolytic Virotherapy in Glioma Tumors

by Sergio Rius-Rocabert, Noemí García-Romero, Antonia García, Angel Ayuso-Sacido and Estanislao Nistal-Villan

Int. J. Mol. Sci. 2020, 21(20), 7604; https://doi.org/10.3390/ijms21207604 - 14 Oct 2020

Cited by 38 | Viewed by 8058

Abstract

Glioma tumors are one of the most devastating cancer types. Glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advances in oncolytic immunotherapy have generated great expectations in the cancer therapy [...] Read more.

Glioma tumors are one of the most devastating cancer types. Glioblastoma is the most advanced stage with the worst prognosis. Current therapies are still unable to provide an effective cure. Recent advances in oncolytic immunotherapy have generated great expectations in the cancer therapy field. The use of oncolytic viruses (OVs) in cancer treatment is one such immune-related therapeutic alternative. OVs have a double oncolytic action by both directly destroying the cancer cells and stimulating a tumor specific immune response to return the ability of tumors to escape the control of the immune system. OVs are one promising alternative to conventional therapies in glioma tumor treatment. Several clinical trials have proven the feasibility of using some viruses to specifically infect tumors, eluding undesired toxic effects in the patient. Here, we revisited the literature to describe the main OVs proposed up to the present moment as therapeutic alternatives in order to destroy glioma cells in vitro and trigger tumor destruction in vivo. Oncolytic viruses were divided with respect to the genome in DNA and RNA viruses. Here, we highlight the results obtained in various clinical trials, which are exploring the use of these agents as an alternative where other approaches provide limited hope. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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21 pages, 386 KiB

Open AccessReview

Oncolytic Viruses as a Platform for the Treatment of Malignant Brain Tumors

by Jana de Sostoa, Valérie Dutoit and Denis Migliorini

Int. J. Mol. Sci. 2020, 21(20), 7449; https://doi.org/10.3390/ijms21207449 - 9 Oct 2020

Cited by 23 | Viewed by 3985

Abstract

Malignant brain tumors remain incurable diseases. Although much effort has been devoted to improving patient outcome, multiple factors such as the high tumor heterogeneity, the strong tumor-induced immunosuppressive microenvironment, and the low mutational burden make the treatment of these tumors especially challenging. Thus, [...] Read more.

Malignant brain tumors remain incurable diseases. Although much effort has been devoted to improving patient outcome, multiple factors such as the high tumor heterogeneity, the strong tumor-induced immunosuppressive microenvironment, and the low mutational burden make the treatment of these tumors especially challenging. Thus, novel therapeutic strategies are urgent. Oncolytic viruses (OVs) are biotherapeutics that have been selected or engineered to infect and selectively kill cancer cells. Increasingly, preclinical and clinical studies demonstrate the ability of OVs to recruit T cells and induce durable immune responses against both virus and tumor, transforming a “cold” tumor microenvironment into a “hot” environment. Besides promising clinical results as a monotherapy, OVs can be powerfully combined with other cancer therapies, helping to overcome critical barriers through the creation of synergistic effects in the fight against brain cancer. Although many questions remain to be answered to fully exploit the therapeutic potential of OVs, oncolytic virotherapy will clearly be part of future treatments for patients with malignant brain tumors. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

22 pages, 299 KiB

Open AccessReview

Efficient Delivery and Replication of Oncolytic Virus for Successful Treatment of Head and Neck Cancer

by Masakazu Hamada and Yoshiaki Yura

Int. J. Mol. Sci. 2020, 21(19), 7073; https://doi.org/10.3390/ijms21197073 - 25 Sep 2020

Cited by 27 | Viewed by 4290

Abstract

Head and neck cancer has been treated by a combination of surgery, radiation, and chemotherapy. In recent years, the development of immune checkpoint inhibitors (ICIs) has made immunotherapy a new treatment method. Oncolytic virus (OV) therapy selectively infects tumor cells with a low-pathogenic [...] Read more.

Head and neck cancer has been treated by a combination of surgery, radiation, and chemotherapy. In recent years, the development of immune checkpoint inhibitors (ICIs) has made immunotherapy a new treatment method. Oncolytic virus (OV) therapy selectively infects tumor cells with a low-pathogenic virus, lyses tumor cells by the cytopathic effects of the virus, and induces anti-tumor immunity to destroy tumors by the action of immune cells. In OV therapy for head and neck squamous cell carcinoma (HNSCC), viruses, such as herpes simplex virus type 1 (HSV-1), vaccinia virus, adenovirus, reovirus, measles virus, and vesicular stomatitis virus (VSV), are mainly used. As the combined use of mutant HSV-1 and ICI was successful for the treatment of melanoma, studies are underway to combine OV therapy with radiation, chemotherapy, and other types of immunotherapy. In such therapy, it is important for the virus to selectively replicate in tumor cells, and to express the viral gene and the introduced foreign gene in the tumor cells. In OV therapy for HNSCC, it may be useful to combine systemic and local treatments that improve the delivery and replication of the inoculated oncolytic virus in the tumor cells. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

22 pages, 828 KiB

Open AccessReview

Adenovirus Receptor Expression in Cancer and Its Multifaceted Role in Oncolytic Adenovirus Therapy

by Lobke C.M. Hensen, Rob C. Hoeben and Selas T.F. Bots

Int. J. Mol. Sci. 2020, 21(18), 6828; https://doi.org/10.3390/ijms21186828 - 17 Sep 2020

Cited by 33 | Viewed by 4694

Abstract

Oncolytic adenovirus therapy is believed to be a promising way to treat cancer patients. To be able to target tumor cells with an oncolytic adenovirus, expression of the adenovirus receptor on the tumor cell is essential. Different adenovirus types bind to different receptors [...] Read more.

Oncolytic adenovirus therapy is believed to be a promising way to treat cancer patients. To be able to target tumor cells with an oncolytic adenovirus, expression of the adenovirus receptor on the tumor cell is essential. Different adenovirus types bind to different receptors on the cell, of which the expression can vary between tumor types. Pre-existing neutralizing immunity to human adenovirus species C type 5 (HAdV-C5) has hampered its therapeutic efficacy in clinical trials, hence several adenoviral vectors from different species are currently being developed as a means to evade pre-existing immunity. Therefore, knowledge on the expression of appropriate adenovirus receptors on tumor cells is important. This could aid in determining which tumor types would benefit most from treatment with a certain oncolytic adenovirus type. This review provides an overview of the known receptors for human adenoviruses and how their expression on tumor cells might be differentially regulated compared to healthy tissue, before and after standardized anticancer treatments. Mechanisms behind the up- or downregulation of adenovirus receptor expression are discussed, which could be used to find new targets for combination therapy to enhance the efficacy of oncolytic adenovirus therapy. Additionally, the utility of the adenovirus receptors in oncolytic virotherapy is examined, including their role in viral spread, which might even surpass their function as primary entry receptors. Finally, future directions are offered regarding the selection of adenovirus types to be used in oncolytic adenovirus therapy in the fight against cancer. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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29 pages, 752 KiB

Open AccessReview

Self-Amplifying RNA Viruses as RNA Vaccines

by Kenneth Lundstrom

Int. J. Mol. Sci. 2020, 21(14), 5130; https://doi.org/10.3390/ijms21145130 - 20 Jul 2020

Cited by 57 | Viewed by 9185

Abstract

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, [...] Read more.

Single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses and rhabdoviruses are characterized by their capacity of highly efficient self-amplification of RNA in host cells, which make them attractive vehicles for vaccine development. Particularly, alphaviruses and flaviviruses can be administered as recombinant particles, layered DNA/RNA plasmid vectors carrying the RNA replicon and even RNA replicon molecules. Self-amplifying RNA viral vectors have been used for high level expression of viral and tumor antigens, which in immunization studies have elicited strong cellular and humoral immune responses in animal models. Vaccination has provided protection against challenges with lethal doses of viral pathogens and tumor cells. Moreover, clinical trials have demonstrated safe application of RNA viral vectors and even promising results in rhabdovirus-based phase III trials on an Ebola virus vaccine. Preclinical and clinical applications of self-amplifying RNA viral vectors have proven efficient for vaccine development and due to the presence of RNA replicons, amplification of RNA in host cells will generate superior immune responses with significantly reduced amounts of RNA delivered. The need for novel and efficient vaccines has become even more evident due to the global COVID-19 pandemic, which has further highlighted the urgency in challenging emerging diseases. Full article

(This article belongs to the Special Issue Oncolytic Virotherapy)

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