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Quantitative and qualitative analyses of the immune responses induced by a multivalent minigene DNA vaccine.

Vaccines containing minigenes - isolated antigenic epitopes encoded by short open reading frames - can, under certain circumstances, confer protective immunity upon the vaccinee. Here we evaluate the efficacy of the minigene vaccine approach using DNA immunization and find that, to be immunogenic, a minigene-encoded epitope requires a perfect "Kozak" translational initiation region. In addition, using intracellular cytokine staining, we show that immunization with a plasmid encoding a full-length protein induces epitope-specific CD8(+) T cells which are detectable directly ex vivo, and constit

Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes.

Pattern-recognition receptors (PRRs) including Toll-like receptors, RIG-I-like receptors, and cytoplasmic DNA receptors are essential for protection against pathogens but require tight control to avert inflammatory diseases. The mechanisms underlying this strict regulation are unclear. MYSM1 was previously described as a key component of epigenetic signaling machinery. We found that in response to microbial stimuli, MYSM1 accumulated in the cytoplasm where it interacted with and inactivated TRAF3 and TRAF6 complexes to terminate PRR pathways for pro-inflammatory and type I interferon responses

An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer.

Chemotherapy resistance and peculiar tumor microenvironment, which diminish or mitigate the effects of therapies, make pancreatic cancer one of the deadliest malignancies to manage and treat. Advanced immunotherapies are under consideration intending to ameliorate the overall patient survival rate in pancreatic cancer. Oncolytic viruses therapy is a new type of immunotherapy in which a virus after infecting and lysis the cancer cell induces/activates patients' immune response by releasing tumor antigen in the blood. The current review covers the pathways and molecular ablation that take place

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… To study the dispersion of virus in the body after intratumoral injection ( 218 ) designed a sodium iodide symporter (NIS) expressing measles virus, which helps in easy CT imaging. 3.2.7 Vesicular Stomatitis Virus Vesicular Stomatitis Virus (VSV) belongs to the Rhabdoviridae family. … The hybrid vesicular stomatitis virus (VSV-FH) armed with F and H envelope proteins of the measles virus shows better anticancer results in preclinical trials. ( 222 ) also tested the efficacy of VSV-FH in in-vitro and in-vivo models of hepatobiliary and pancreatic cancer. …

Combinatorial Approaches for Cancer Treatment Using Oncolytic Viruses: Projecting the Perspectives through Clinical Trials Outcomes.

Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials eva

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… Several rhabdoviruses have been studied for oncolytic properties, among which vesicular stomatitis virus (VSV) and Maraba virus. Vesicular stomatitis virus (VSV) seems quite promising as a safe and effective oncolytic virus, especially in combination with different immunotherapeutic approaches. … Experimental Evolution Generates Novel Oncolytic Vesicular Stomatitis Viruses with Improved Replication in Virus-Resistant Pancreatic Cancer Cells. J. Virol. 2020;94:e01643-19. doi: 10.1128/JVI.01643-19. 27. Altomonte J., Marozin S., Schmid R.M., Ebert O. …

Oncogenes: The Passport for Viral Oncolysis Through PKR Inhibition.

The transforming properties of oncogenes are derived from gain-of-function mutations, shifting cell signaling from highly regulated homeostatic to an uncontrolled oncogenic state, with the contribution of the inactivating mutations in tumor suppressor genes P53 and RB, leading to tumor resistance to conventional and target-directed therapy. On the other hand, this scenario fulfills two requirements for oncolytic virus infection in tumor cells: inactivation of tumor suppressors and presence of oncoproteins, also the requirements to engage malignancy. Several of these oncogenes have a negative i

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… stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity, and enhance oncolytic potency Cancer Res 2014 74 13 3567 3578 24812275 10.1158/0008-5472.CAN-13-3306 46 Patel MR Jacobson BA Ji Y Vesicular stomatitis virus expressing interferon-β is oncolytic and promotes antitumor immune responses … Malilas W Koh SS Srisuttee R Cancer upregulated gene 2, a novel oncogene, confers resistance to oncolytic vesicular stomatitis virus through STAT1-OASL2 signaling Cancer Gene Ther 2013 20 2 125 132 23306614 10.1038/cgt.2012.96 117 Thomas MA Spencer JF Toth K Sagartz JE Phillips NJ Wold WS Immunosuppression …

Medical countermeasures against henipaviruses: a review and public health perspective.

Henipaviruses, including Nipah virus, are regarded as pathogens of notable epidemic potential because of their high pathogenicity and the paucity of specific medical countermeasures to control infections in humans. We review the evidence of medical countermeasures against henipaviruses and project their cost in a post-COVID-19 era. Given the sporadic and unpredictable nature of henipavirus outbreaks, innovative strategies will be needed to circumvent the infeasibility of traditional phase 3 clinical trial regulatory pathways. Stronger partnerships with scientific institutions and regulatory au

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… NiV-M=Nipah virus Malaysia. rVSV=recombinant vesicular stomatitis virus. VSV=vesicular stomatitis virus. … NiV-M=Nipah virus Malaysia. rVSV=recombinant vesicular stomatitis virus. VSV=vesicular stomatitis virus. …

Trial watch: Oncolytic viruses for cancer therapy.

Oncolytic virotherapy is emerging as a promising approach for the treatment of several neoplasms. The term "oncolytic viruses" is generally employed to indicate naturally occurring or genetically engineered attenuated viral particles that cause the demise of malignant cells while sparing their non-transformed counterparts. From a conceptual standpoint, oncolytic viruses differ from so-called "oncotropic viruses" in that only the former are able to kill cancer cells, even though both display a preferential tropism for malignant tissues. Of note, such a specificity can originate at several diffe

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… stomatitis virus. … stomatitis virus using measles virus envelope glycoproteins Hum Gene Ther 2012 23 484 91 10.1089/hum.2011.146 22171635 PMC3360499 16 Muik A Kneiske I Werbizki M Wilflingseder D Giroglou T Ebert O Pseudotyping vesicular stomatitis virus with lymphocytic choriomeningitis virus glycoproteins enhances …

The Oncolytic Virotherapy Era in Cancer Management: Prospects of Applying H-1 Parvovirus to Treat Blood and Solid Cancers.

Non-Hodgkin lymphoma (NHL) and leukemia are among the most common cancers worldwide. While the treatment of NHL/leukemia of B-cell origin has much progressed with the introduction of targeted therapies, few treatment standards have been established for T-NHL/leukemia. As presentation in both B- and T-NHL/leukemia patients is often aggressive and as prognosis for relapsed disease is especially dismal, this cancer entity poses major challenges and requires innovative therapeutic approaches. In clinical trials, oncolytic viruses (OVs) have been used against refractory multiple myeloma (MM). In pr

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… MM, multiple myeloma; AML, acute myeloid leukemia; B-L, B-lymphocyte; T-L, T-lymphocyte; CVA21, coxsackie virus A21; VSV, vesicular stomatitis virus; CLL, chronic lymphocytic leukemia . … Targeting the apoptotic pathway with BCL-2 inhibitors sensitizes primary chronic lymphocytic leukemia cells to vesicular stomatitis virus-induced oncolysis . …

Targeted disruption of IRF-1 or IRF-2 results in abnormal type I IFN gene induction and aberrant lymphocyte development.

Interferon regulatory factor 1 (IRF-1), a transcriptional activator, and its antagonistic repressor, IRF-2, were originally identified as regulators of the type I interferon (IFN) system. We have generated mice deficient in either IRF-1 or IRF-2 by gene targeting in embryonic stem cells. IRF-1-deficient fibroblasts lacked the normally observed type I IFN induction by poly(I):poly(C), while they induced type I IFN to similar levels as the wild type following Newcastle disease virus (NDV) infection. In contrast, IRF-2-deficient fibroblasts showed up-regulated type I IFN induction by NDV infectio

Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study.

BACKGROUND: The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. METHODS: In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18-61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscu…

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!).

BACKGROUND: rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa. METHODS: We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a si…

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

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… Vesicular stomatitis virus (VSV) can selectively infect endothelial cells in the tumor microenvironment and cause thrombosis in the tumor vessels [ 22 ]. … Stomatitis Virus. …

Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.

Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs). Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish th

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… Clinical Trials for Oncolytic Virus-Related Therapy In the past two decades, >3000 patients enrolled in clinical trials using oncolytic viruses, including adenovirus, herpesvirus, picornavirus, measles virus, vaccinia virus, reovirus, poliovirus, coxsackievirus, vesicular stomatitis virus, parvovirus … stomatitis virus (VSVDeltaM51) | IL-15 | NKT | pancreatic cancer | Nelson (2022) [ 108 ] HSV-1 (G47Δ) | N/A | Lp2-CAR-T | glioblastoma | Chalise (2022) [ 83 ] Vesicular stomatitis virus, reovirus | mIFNβ (VSV) | mEGFRvIII | murine melanoma, glioma | Evgin (2022) [ 3 , 85 ] HSV-1 | OX40L, IL-12 | TILs …

Viral warfare: unleashing engineered oncolytic viruses to outsmart cancer's defenses.

Oncolytic virotherapy (OVT) has emerged as a promising and innovative cancer treatment strategy that harnesses engineered viruses to selectively infect, replicate within, and destroys malignant cells while sparing healthy tissues. Beyond direct oncolysis, oncolytic viruses (OVs) exploit tumor-specific metabolic, antiviral, and immunological vulnerabilities to reshape the tumor microenvironment (TME) and initiate systemic antitumor immunity. Despite promising results from preclinical and clinical studies, several barriers, including inefficient intratumoral virus delivery, immune clearance, and

Oncolytic virus-based hepatocellular carcinoma treatment: Current status, intravenous delivery strategies, and emerging combination therapeutic solutions.

Current treatments for advanced hepatocellular carcinoma (HCC) have limited success in improving patients' quality of life and prolonging life expectancy. The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies. Recently, there has been increased interest in oncolytic viruses (OVs) as a therapeutic modality for HCC. OVs undergo selective replication in cancerous tissues and kill tumor cells. Strikingly, pexastimogene devacirepvec (Pexa-Vec) was granted an orphan drug status in HCC by the U.S. Food and Drug Administration (FDA) in 2013.

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… Vesicular stomatitis virus (VSV) VSV is a negative-strand RNA virus with an envelope with an inherent ability to infect cancer cells [81] . … Oncolytic vesicular stomatitis virus for treatment of orthotopic hepatocellular carcinoma in immune-competent rats Cancer Res 63 13 2003 3605 3611 12839948 82 Ebert O. Shinozaki K. Kournioti C. Park M.S. Garcia-Sastre A. Woo S.L. …

A Comprehensive Review of Modern Cancer Therapies Utilizing Oncolytic Viruses.

Oncolytic viruses (OVs) are gaining traction as advanced tools in cancer therapy. They are distinguished by their ability to destroy malignant cells while sparing normal tissue specifically. In addition to their direct tumor-lysing properties, an essential benefit of oncolytic virus therapy is its capacity to activate both the innate and adaptive immune systems. To enhance these therapeutic actions, many OVs have been genetically engineered to encode immune-modulating factors that reestablish or strengthen antitumor immune responses. Recent studies show that combining OVs with other forms of i

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… In contrast, single-stranded RNA viruses are divided into two categories: positive-sense (such as coxsackievirus and poliovirus) and negative-sense (including measles virus, Newcastle Disease virus, and vesicular stomatitis virus) ( Figure 2 ). … Vesicular Stomatitis Virus Vesicular stomatitis virus (VSV) is a member of the Rhabdoviridae family and is classified as a negative-sense RNA virus. Its genome is relatively compact, consisting of about 11,000 nucleotides and encoding five different viral proteins. …

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

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… Vesicular stomatitis virus Owing to the inherent deficiencies in IFN signaling within malignant cells, vesicular stomatitis virus (VSV) intrinsically demonstrates tumor selectivity, enabling preferential oncolysis while preserving normal tissues. … Vesicular stomatitis virus Silent information regulator sirtuin 1 (SIRT1), tightly regulated by the oncogenic microRNA miR-34a, is a pivotal determinant of VSV susceptibility in tumor cells 284 . …

Oncolytic viruses on the cusp of success?: proceedings of the 9th International Conference on Oncolytic Virus Therapeutics

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… Juan Corredo (University of Calgary, Canada) explained how high-risk neuroblastoma–associated N-myc overexpression downregulates interferon (IFN)-stimulated gene expression, which sensitizes neuroblastoma cells to vesicular stomatitis virus (VSV) replication. … Retargeting Oncolytic Vesicular Stomatitis Virus to Human T-Cell Lymphotropic Virus Type 1-Associated Adult T-Cell Leukemia. J Virol 89: 11786–11800. Tedcastle, A, Illingworth, S, Brown, A, Seymour, LW and Fisher, KD (2016). …

Oncolytic virotherapy as emerging immunotherapeutic modality: potential of parvovirus h-1.

Human tumors develop multiple strategies to evade recognition and efficient suppression by the immune system. Therefore, a variety of immunotherapeutic strategies have been developed to reactivate and reorganize the human immune system. The recent development of new antibodies against immune check points may help to overcome the immune silencing induced by human tumors. Some of these antibodies have already been approved for treatment of various solid tumor entities. Interestingly, targeting antibodies may be combined with standard chemotherapy or radiation protocols. Furthermore, recent evide

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… These include Parvovirus, Adenovirus, Vesicular Stomatitis Virus, Reovirus, NDV, Measles Virus, Seneca Valley Virus, Poliovirus, and Coxsackie Virus (Table 1 ). Table 1 Oncolytic viruses . Oncolytic viruses in clinical trials (ds, double stranded; ss, single stranded) . … Viral Immunol ( 2009 ) 22 ( 6 ): 353 – 69 10.1089/vim.2009.0057 19951173 PMC2812813 40 Saloura V Wang LC Fridlender ZG Sun J Cheng G Kapoor V Evaluation of an attenuated vesicular stomatitis virus vector expressing interferon-beta for use in malignant pleural mesothelioma: heterogeneity in interferon …