Oncolytic Herpes Viruses as a Potential Mechanism for Cancer Therapy

Lou, Emil

doi:10.1080/0284186031000518

Cited by 27 publications

(29 citation statements)

References 123 publications

(78 reference statements)

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“…17 Oncolytic replication of a virus is an immunogenic event 69 that generates a response against both viral and tumor antigens. 70,71 Herpes simplex viruses induce antitumor immunity by activation of dendritic cells via Toll-like receptors 2 and 9, which in turn enhance antigen presentation and specific T and B lymphocyte responses. [72][73][74] In addition, herpes simplex virus reduces the number of myeloid-derived suppressor cells, which contribute to tumor cells' ability to circumvent host immune surveillance.…”

Section: X400 X400mentioning

confidence: 99%

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

et al. 2011

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Oncolytic viruses are a promising method of cancer therapy, even for advanced malignancies. HF10, a spontaneously mutated herpes simplex type 1, is a potent oncolytic agent. The interaction of oncolytic herpes viruses with the tumor microenvironment has not been well characterized. We injected HF10 into tumors of patients with recurrent breast carcinoma, and sought to determine its effects on the tumor microenvironment. Six patients with recurrent breast cancer were recruited to the study. Tumors were divided into two groups: saline-injected (control) and HF10-injected (treatment). We investigated several parameters including neovascularization (CD31) and tumor lymphocyte infiltration (CD8, CD4), determined by immunohistochemistry, and apoptosis, determined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Median apoptotic cell count was lower in the treatment group (P ¼ 0.016). Angiogenesis was significantly higher in treatment group (P ¼ 0.032). Count of CD8-positive lymphocytes infiltrating the tumors was higher in the treatment group (P ¼ 0.008). We were unable to determine CD4-positive lymphocyte infiltration. An effective oncolytic viral agent must replicate efficiently in tumor cells, leading to higher viral counts, in order to aid viral penetration. HF10 seems to meet this criterion; furthermore, it induces potent antitumor immunity. The increase in angiogenesis may be due to either viral replication or the inflammatory response.

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Section: X400 X400mentioning

confidence: 99%

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

et al. 2011

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“…166 The safety of G207 has been tested extensively in animal models from mice to non-human primates. [167][168][169][170] No virus-related toxicities was observed at doses as high as 10 9 PFU in monkeys, 167 125,[171][172][173][174][175][176][177] The existence of pre-existing anti-HSV-1 immunity has no measurable effect on the oncolytic activity of G207, and multiple injections can be applied without being affected by immune resistance to the virus. 178,179 It appears that G207 inhibits tumor growth by two mechanisms: direct oncolysis via virus replication 166 and induction of tumor-specific immunity via an increase in cytotoxic T-cell (CTL) activity.…”

Section: Hsv-1 For Cancer Treatment Y Shen and J Nemunaitismentioning

confidence: 99%

“…110,124 Many replication-conditional HSV-1 vectors have included mutations and/or deletions in one or more of the genes encoding thymidine kinase, DNA polymerase, uracil DNA glycosylase, ribonucleotide reductase (RR), and ICP34.5. 125 The second approach is to limit the expression of a critical viral gene to tumor tissues through the use of tumor-and/or tissue-specific promoters, represented by the adenovirus mutant CV706. 126,127 The third approach is to alter viral tropism through modification of surface proteins.…”

Section: Conditionally Replicating Herpes Simplex Virus Type 1 Vectormentioning

confidence: 99%

Herpes simplex virus 1 (HSV-1) for cancer treatment

2006

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Cancer remains a serious threat to human health, causing over 500 000 deaths each year in US alone, exceeded only by heart diseases. Many new technologies are being developed to fight cancer, among which are gene therapies and oncolytic virotherapies. Herpes simplex virus type 1 (HSV-1) is a neurotropic DNA virus with many favorable properties both as a delivery vector for cancer therapeutic genes and as a backbone for oncolytic viruses. Herpes simplex virus type 1 is highly infectious, so HSV-1 vectors are efficient vehicles for the delivery of exogenous genetic materials to cells. The inherent cytotoxicity of this virus, if harnessed and made to be selective by genetic manipulations, makes this virus a good candidate for developing viral oncolytic approach. Furthermore, its large genome size, ability to infect cells with a high degree of efficiency, and the presence of an inherent replication controlling mechanism, the thymidine kinase gene, add to its potential capabilities. This review briefly summarizes the biology of HSV-1, examines various strategies that have been used to genetically modify the virus, and discusses preclinical as well as clinical results of the HSV-1-derived vectors in cancer treatment.

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“…A replication-competent controlled virus may be derived from an HSV-1 (or an HSV-2) wild-type virus. This choice is motivated by the following considerations [73][74][75]: the virus has a double-stranded DNA genome (of >150 kbp) that is replicated by a high-fidelity polymerase, remains episomal, tolerates sizable insertions as well as supports stable expression of passenger genes and can readily be manipulated (e.g., [76]); the virus infects a wide range of host cells and causes efficient lysis; that it latently infects sensory nerve cells is seen as a manageable complication (see below); the virus is endemic in the human population, but pre-existing immunity does not appear to substantially interfere with its use as an immunization agent; the virus causes lethality only in exceptional circumstances and responds to drugs such as acyclovir and replication of the virus is highly efficient, and high titers are reached in vitro.…”

Section: Hivmentioning

confidence: 99%

A novel approach for addressing diseases not yielding to effective vaccination? Immunization by replication-competent controlled virus

Voellmy

Bloom

Vilaboa

2015

Expert Review of Vaccines

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Vaccination involves inoculation of a subject with a disabled disease-causing microbe or parts thereof. While vaccination has been highly successful, we still lack sufficiently effective vaccines for important infectious diseases. We propose that a more complete immune response than that elicited from a vaccine may be obtained from immunization with a disease-causing virus modified to subject replication-essential genes to the control of a gene switch activated by non-lethal heat in the presence of a drug-like compound. Upon inoculation, strictly localized replication of the virus would be triggered by a heat dose administered to the inoculation site. Activated virus would transiently replicate with an efficiency approaching that of the disease-causing virus and express all viral antigens. It may also vector heterologous antigens or control co-infecting microbes.

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Oncolytic Herpes Viruses as a Potential Mechanism for Cancer Therapy

Cited by 27 publications

References 123 publications

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

Impact of novel oncolytic virus HF10 on cellular components of the tumor microenviroment in patients with recurrent breast cancer

Herpes simplex virus 1 (HSV-1) for cancer treatment

A novel approach for addressing diseases not yielding to effective vaccination? Immunization by replication-competent controlled virus

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