Oncolytic HSV Vectors and Anti-Tumor Immunity

Cohen, Justus B.; Goins, William F.; Hall, Bonnie L.; Jackson, Joseph W.; Kohanbash, Gary; Amankulor, Nduka; Kaur, Balveen; Caligiuri, Michael A.; Chiocca, E. Antonio; Holland, Eric C.; Quéva, Christophe

doi:10.21775/9781913652555.11

Cited by 3 publications

(10 citation statements)

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“…The HSV genome comprises several essential and nonessential genes that can be modified to ensure selective replication in cancer cells while sparing normal cells. 16 The frequently mutated gene to engineer HSV is γ34.5a pivotal determinant for viral neuropathogenicity. When HSV infects normal cells, protein kinase R (PKR) phosphorylates eukaryotic translation initiation factor-alpha (eIF2α) and prevents viral protein synthesis.…”

Section: Unarmed Ohsvs For Gbmmentioning

confidence: 99%

“…15 The highly stable genome, potent cytolytic capability, convenience in genome engineering, and availability of effective antiherpetic drugs to treat adverse reactions make oHSV an attractive class of anticancer therapeutic. 16 The first genetically modified oHSV for glioma treatment was reported in 1991. 17 Since then, many oHSVs such as unarmed -genetically modified oHSVs but not armed with transgene, re-targeted -genetically altered for tumor receptor-specific viral entry, and armed -engineered to express therapeutic transgene variants, etc., have been developed and tested in GBM preclinically, either alone or in combination with other anti-cancer agents (Table 1-3, Figure 1-3).…”

Section: Introductionmentioning

confidence: 99%

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The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment

Nguyen¹,

Saha²

2021

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Glioblastoma (GBM) is a lethal primary malignant brain tumor with no current effective treatments. The recent emergence of immuno-virotherapy and FDA approval of T-VEC have generated a great expectation towards oncolytic herpes simplex viruses (oHSVs) as a promising treatment option for GBM. Since the generation and testing of the first genetically engineered oHSV in glioma in the early 1990s, oHSV-based therapies have shown a long way of great progress in terms of anti-GBM efficacy and safety, both preclinically and clinically. Here, we revisit the literature to understand the recent advancement of oHSV in the treatment of GBM. In addition, we discuss current obstacles to oHSV-based therapies and possible strategies to overcome these pitfalls.

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Section: Unarmed Ohsvs For Gbmmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment

Nguyen¹,

Saha²

2021

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“…Traditionally, the main genetic engineering techniques used to generate HSV mutants include homologous recombination, cell transfection and bacterial artificial chromosome technology (6). Initially, genetically engineered viruses are constructed by deleting or mutating one or more of the HSV-1 genes (10). Conversely, there are double copies of multiple genes, such as ICP34.5, ICP4 and ICP0, which complicate the genetic manipulation of HSV-1 and limit the development of oHSVs but also provide more possibilities, such as oHSVs with a single copy of γ34.5, ensuring the safety of normal nerve cells while maintaining the antitumor effect (8).…”

Section: Engineering Novel Ohsvsmentioning

confidence: 99%

“…Thus, improved treatment for GBM, with their multiple oncogenic pathways and refractory nature, requires a multimodal approach. Recent studies have reported that the combination of an oHSV and multiple anticancer modalities is often more effective than any single treatment alone for GBM, as with other malignancies (10,17).…”

Section: Engineering Novel Ohsvsmentioning

confidence: 99%

“…Only rapidly proliferating tumor cells, which do not express the precursors for viral DNA synthesis found in normal cells, can promote HSV replication without the presence of nucleotide-metabolizing enzymes, explaining why oncolytic viruses (OVs) can target tumors (6). Engineered oHSVs can directly destroy tumor cells by selectively replicating in them (oncolysis), altering the tumor microenvironment and stimulating antitumor immune responses, which are the main mechanisms by which OVs kill cancer cells (10). Conversely, anti-HSV agents, including ganciclovir and acyclovir, can ensure the safety of oHSV in clinical use (6).…”

Section: Introductionmentioning

confidence: 99%

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Multiple strategies to improve the therapeutic efficacy of oncolytic herpes simplex virus in the treatment of glioblastoma (Review)

et al. 2021

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Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses

Stanfield

Kousoulas

Fernández³

et al. 2021

Viruses

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Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.

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Oncolytic HSV Vectors and Anti-Tumor Immunity

Cited by 3 publications

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The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment

The Current State of Oncolytic Herpes Simplex Virus for Glioblastoma Treatment

Multiple strategies to improve the therapeutic efficacy of oncolytic herpes simplex virus in the treatment of glioblastoma (Review)

Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses

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