Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus.

Ochiai, Hidenobu; Campbell, Stephanie A.; Archer, Gary E.; Chewning, Tracy A.; Dragunsky, Eugenia; Ivanov, Alexander P.; Gromeier, Matthias; Sampson, John H.

doi:10.1158/1078-0432.ccr-05-1595

Cited by 54 publications

(49 citation statements)

References 31 publications

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“…We have in the past described a poliovirus/HRV2 chimera [PV1(RIPO) or PVS(RIPO)] that seems to meet this requirement. PVS(RIPO) is, in fact, under consideration for brain tumor therapy (7,8). 1 With the exception of Raji cells, a Burkitt's lymphoma cell line harboring a transcriptionally inactive CD155 gene (31), wt poliovirus kills all human tumor cells tested, including neuroblastoma cell lines established from patients (17).…”

Section: Discussionmentioning

confidence: 99%

“…Poliovirus has recently been added to the list of viruses that hold promise as possible agents in tumor therapy (7,8). A nonenveloped, plus-stranded enterovirus of the Picornaviridae, poliovirus replicates in the gastrointestinal tract causing little, if any, clinical symptoms.…”

Section: Introductionmentioning

confidence: 99%

“…In poliovirus, an exchange of the internal ribosomal entry site (IRES) within the 5 ¶-nontranslated region (NTR) with its counterpart from human rhinovirus type 2 (HRV2), another picornavirus, yielded viruses [called PV1 (RIPO)] that are highly attenuated in transgenic mice for the human poliovirus receptor (PVR) CD155 (CD155 tg mice; refs. 10, 12) yet replicate efficiently and lytically in cell lines derived from malignant glioma and breast cancer (7,8,10,13). However, PV1(RIPO) and PVS(RIPO), a derivative of PV1(RIPO) that is currently under investigation for the treatment of glioma, grow poorly in neuroblastoma cells (7,10).…”

Section: Introductionmentioning

confidence: 99%

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Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model

et al. 2007

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Neuroblastoma is one of the most common solid tumors in children. Treatment is of limited utility for high-risk neuroblastoma and prognosis is poor. Resistance of neuroblastoma to conventional therapies has prompted us to search for a novel therapeutic approach based on genetically modified polioviruses. Poliovirus targets motor neurons leading to irreversible paralysis. Neurovirulence can be attenuated by point mutations or by exchange of genetic elements between different picornaviruses. We have developed a novel and stable attenuated poliovirus, replicating in neuroblastoma cells, by engineering an indigenous replication element (cre), copied from a genome-internal site, into the 5 ¶-nontranslated genomic region (mono-crePV). An additional host range mutation (A 133 G) conferred replication in mouse neuroblastoma cells (Neuro-2a CD155 ) expressing CD155, the poliovirus receptor. Crossing immunocompetent transgenic mice susceptible to poliovirus (CD155 tg mice) with A/J mice generated CD155 tgA/J mice, which we immunized against poliovirus. Neuro-2a CD155 cells were then transplanted into these animals, leading to lethal tumors. Despite preexisting high titers of anti-poliovirus antibodies, established lethal s.c. Neuro2a CD155 tumors in CD155 tgA/J mice were eliminated by intratumoral administrations of A 133 Gmono-crePV. No signs of paralysis were observed. Interestingly, no tumor growth was observed in mice cured of neuroblastoma that were reinoculated s.c. with CD155 . This result indicates that the destruction of neuroblastoma cells by A 133 Gmono-crePV may lead to a robust antitumor immune response. We suggest that our novel attenuated oncolytic poliovirus is a promising candidate for effective oncolytic treatment of human neuroblastoma or other cancer even in the presence of present or induced antipolio immunity. [Cancer Res 2007;67(6):2857-64]

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model

et al. 2007

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“…The HRV2 IRES produces neuron-specific growth defects (3, 16) but does not affect propagation in established (18) and primary (36) GBM cell lines. PV/HRV2 chimeras efficiently reduce the tumor burden in GBM xenograft animal models (18,44). Specificity for GBM is attributed to neuronal repressors of HRV2 IRES function, the dsRNA binding protein 76 (DRBP76) and nuclear factor 45 (NF45) (37,38).…”

mentioning

confidence: 99%

Attenuation of Herpes Simplex Virus Neurovirulence with Picornavirus cis -Acting Genetic Elements

Campbell

Mulvey

Mohr

et al. 2007

J Virol

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Viral pathogenesis depends on a suitable milieu in target host cells permitting viral gene expression, propagation, and spread. In many instances, viral genomes can be manipulated to select for propagation in certain tissues or cell types. This has been achieved for the neurotropic poliovirus (PV) by exchange of the internal ribosomal entry site (IRES), which is responsible for translation of the uncapped plus-strand RNA genome. The IRES of human rhinovirus type 2 (HRV2) confers neuron-specific replication deficits to PV but has no effect on viral propagation in malignant glioma cells. We report here that placing the critical ␥ 1 34.5 virulence genes of herpes simplex virus type 1 (HSV) under translation control of the HRV2 IRES results in neuroattenuation in mice. In contrast, IRES insertion permits HSV propagation in malignant glioma cell lines that do not support replication of HSV recombinants carrying ␥ 1 34.5 deletions. Our observations indicate that the conditions for alternative translation initiation at the HRV2 IRES in malignant glioma cells differ from those in normal central nervous system (CNS) cells. Picornavirus regulatory sequences mediating cell typespecific gene expression in the CNS can be utilized to target cancerous cells at the level of translation regulation outside their natural context. Herpes simplex virus type 1 (HSV) and poliovirus (PV) are neuropathogens that target cells in the central nervous system (CNS). Both use cellular receptors belonging to the nectin family: nectin-1 or the PV receptor-related molecule 1 for HSV (15) and CD155 or the PV receptor for PV (35). Both viruses have been genetically engineered to attenuate neuropathogenicity. Nonneurovirulent variants of both HSV and PV selectively propagate in malignant glioma cells and are being investigated as oncolytic agents against glioblastoma multiforme (GBM).The HSV double-stranded DNA (dsDNA) genome of ϳ152,250 bp encodes at least 84 gene products. Attenuation was achieved by deletion of the ␥ 1 34.5 gene, abolishing neurovirulence in mice (2, 5) and primates (21). Moreover, ⌬␥ 1 34.5 HSVs, either with or without a mutation in another nonessential gene, have been safely administered to GBM patients (32, 48). A key function of the ␥ 1 34.5 gene product, infected-cell protein 34.5 (ICP34.5), is to oppose host antiviral responses that culminate in protein synthesis shutoff. HSV infection results in dsRNA-dependent protein kinase (PKR) activation, which unchecked, arrests translation via phosphorylation of the ␣ subunit of eukaryotic initiation factor (eIF-2␣) (4, 6). ICP34.5 redirects cellular protein phosphatase 1␣ to dephosphorylate eIF-2␣, maintaining a pool of active eIF-2␣ (19). ⌬␥ 1 34.5 mutants are unable to counter PKR, and viral growth is therefore inhibited in the CNS (4, 6). However, these mutants propagate efficiently in tumor cells with defective or suppressed PKR responses (1), spurring clinical application as oncolytic agents (32,48). ⌬␥ 1 34.5 growth is impeded in some cancer cell lines (39, 50), indicating t...

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“…As shown by us and other investigators, pathogenesis of neurotropic viruses including poliovirus can be controlled by translation (Gromeier et al, 1996(Gromeier et al, , 2000Mohr, 2005). In poliovirus, an exchange of the internal ribosomal entry site (IRES) within the 5'-nontranslated region (NTR) with its counterpart from human rhinovirus type 2 (HRV2), another picornavirus, yielded viruses [called PV1 (RIPO)] that are highly attenuated in mice transgenic for the human poliovirus receptor (PVR) CD155 (CD155 tg mice; Gromeier et al, 1996Gromeier et al, , 1999 yet replicate efficiently and lytically in cell lines derived from malignant glioma and breast cancer (Cello et al, 2008;Gromeier et al, 1996Gromeier et al, , 2000Ochiai et al, 2004Ochiai et al, , 2006. However, PV1(RIPO) and PVS(RIPO), a derivative of PV1(RIPO) that is currently under investigation for the treatment of glioma, grow poorly in neuroblastoma cells (Cello et al, 2008;Gromeier et al, 1996Gromeier et al, , 2000).…”

Section: Oncolytic Poliovirus For Treatment Of Neuroblastoma: Preclinmentioning

confidence: 99%

Oncolytic Poliovirus Therapy in a Mouse Model of Neuroblastoma: Preclinical Data Analysis and Future Studies

Toyoda¹,

Wimmer²,

Cello³

2012

Neuroblastoma - Present and Future

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Targeted therapy for glioblastoma multiforme neoplastic meningitis with intrathecal delivery of an oncolytic recombinant poliovirus.

Cited by 54 publications

References 31 publications

Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model

Oncolytic Treatment and Cure of Neuroblastoma by a Novel Attenuated Poliovirus in a Novel Poliovirus-Susceptible Animal Model

Attenuation of Herpes Simplex Virus Neurovirulence with Picornavirus cis -Acting Genetic Elements

Oncolytic Poliovirus Therapy in a Mouse Model of Neuroblastoma: Preclinical Data Analysis and Future Studies

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