Enhancement of Th2 responses to replicative herpes simplex virus type 1 vectors by immunomodulative chemotherapy

Peltoniemi, Jutta; Broberg, Eeva; Nygårdas, Michaela; Erälinna, Juha-Pekka; Waris, Matti; Hukkanen, Veijo

doi:10.1016/j.intimp.2005.12.003

Cited by 5 publications

(4 citation statements)

References 47 publications

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“…As observed earlier, R3659 is able to induce Th2 responses by itself, explaining the effects of the HSV backbone. 28,51,68 This study also supports previous studies, 26,27,29,69 indicating that HSV vectors are good candidates for gene therapy of CNS diseases. Still, it is important to study the safety of these vectors and also optimize the expression efficiency in the target tissue.…”

Section: Hsv-1 Expressing Il-5 Ameliorates Eae M Nygårdas Et Alsupporting

confidence: 88%

“…The virus R3659 and genomic structure of the cytokine-expressing HSV vectors have been described before. 29,68,71 Cytokine expression from the HSV vectors expressing IL-10 and IL-5 was tested from supernatants with EIA (eBioscience, San Diego, CA, USA). Shortly, CSM rat neuronal cells were infected with R8308 and R8316 and supernatants were collected.…”

Section: Viral Vectorsmentioning

confidence: 99%

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Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

et al. 2011

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Experimental autoimmune encephalomyelitis (EAE) is an autoimmune inflammation of the central nervous system and is used as the experimental model of multiple sclerosis (MS). The exact mechanism behind the disease is still unknown, but interleukin (IL)-17 expressing T cells are thought to mediate the disease. Toll-like receptors (TLRs) are known to have a role in the innate immune response against pathogens, and several TLRs have also a role in the disease course of EAE. Here, we show that treatment with a herpes simplex virus type 1 vector expressing the Th2 cytokine IL-5 ameliorates EAE and decreases the numbers of infiltrating lymphocytes in the brain. The effect involves downregulation of TLR 2, 3 and 9 mRNA expression and upregulation of type I interferons (IFNs) in brains during onset of disease. The elevated expression of type I IFNs was also observed during recovery.

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Section: Hsv-1 Expressing Il-5 Ameliorates Eae M Nygårdas Et Alsupporting

confidence: 88%

Section: Viral Vectorsmentioning

confidence: 99%

Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

et al. 2011

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“…To prolong the effect of transgenes expressed from viral vectors in gene transfer therapy, it has been shown that treatment with cyclosporine A can reduce the inflammatory response to a HSV vector leading to improved transgene expression [331], while immunomodulative treatment with Linomide seems to facilitates the spread and expression of ICP34.5-negative vector in CNS [332]. …”

Section: Factors That May Affect Hsv Vectors Efficacymentioning

confidence: 99%

HSV Recombinant Vectors for Gene Therapy

Manservigi

Argnani²,

Marconi³

2010

TOVJ

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The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.

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Section: Factors That May Affect Hsv Vectors Efficacymentioning

confidence: 99%

HSV Recombinant Vectors for Gene Therapy~!2009-12-17~!2010-13-31~!2010-06-17~!

Manservigi¹,

Argnani²,

Marconi³

2010

TOVJ

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Abstract:The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.Keywords: HSV, viral vectors, oncolytic vectors, gene therapy, neurodegenerative disorders, cancer, targeting, vaccines. THE HERPES SIMPLEX VIRUS LIFE CYCLEHerpes simplex virus (HSV) is an enveloped, doublestranded (ds) DNA virus [1]. The mature virion consists of different components: an external envelope containing about 13 glycoproteins involved in different functions, among which the first steps of binding and entry into the host cell; an amorphous layer known as the tegument, containing some 20 different proteins with structural and regulatory roles; and an icosadeltahedral capsid containing a toroidal dsDNA. The HSV-1 genome consists of 152 kb of linear, dsDNA arranged as long and short unique segments (UL and US) flanked by inverted repeated sequences (TRL/IRL and IRS/TRS, respectively) (Fig. 1). The repeated regions of the viral genome contain two immediate-early (IE) genes [infected cell protein (ICP) 4 and ICP0], a late (L) gene (ICP34.5) and the latency associated transcripts (LAT) that are each present in two copies. Thus, the repeated region located between the long and short segments of the genome (the joint repeat region) contains a single copy of each gene. HSV genome encodes approximately 90 genes that can be classified as essential or nonessential based on their requirement for virus replication in tissue culture. Essential genes are required for virus growth such that viral mutants lacking these genes can only establish a lytic infection if the missing genes are supplied in trans by an engineered c...

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Enhancement of Th2 responses to replicative herpes simplex virus type 1 vectors by immunomodulative chemotherapy

Cited by 5 publications

References 47 publications

Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

Treatment of experimental autoimmune encephalomyelitis in SJL/J mice with a replicative HSV-1 vector expressing interleukin-5

HSV Recombinant Vectors for Gene Therapy

HSV Recombinant Vectors for Gene Therapy~!2009-12-17~!2010-13-31~!2010-06-17~!

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