Attenuated multi–mutated herpes simplex virus–1 for the treatment of malignant gliomas

Mineta, Toshihiro; Rabkin, Samuel D.; Yazaki, Takahito; Hunter, William D.; Martuza, Robert L.

doi:10.1038/nm0995-938

Cited by 746 publications

(632 citation statements)

References 29 publications

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“…Clinical testing using this approach includes the use of adenoviruses, where the E1A region of the virus is driven by a prostate-specific promoter. 14 Clinical testing with viruses in which pathways blocking the anti-viral response have been disabled has used adenoviruses in which the E1B region has been deleted (ONYX-O15) 15 and herpesviruses in which the ICP34.5 gene (the so-called 'neurovirulence factor') has been removed (1716 and G207 [G207 is also deleted for the ICP6 gene encoding ribonucleotide reductase necessary for growth in neurons but dispensable in other cells] 16,17 ). The adenovirus E1B region is required for virus replication in cells with a functional p53 pathway, but is dispensable in most tumour cells where the p53 or related pathways are disrupted (eg see reference 18).…”

Section: Introductionmentioning

confidence: 99%

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

Liu¹,

Robinson²,

Han³

et al. 2003

Gene Ther

707

624

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Section: Introductionmentioning

confidence: 99%

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

Liu¹,

Robinson²,

Han³

et al. 2003

Gene Ther

707

624

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“…Therefore, G207 maintains sensitivity to acyclovir and ganciclovir. 54 Generally, G207 has been studied in brain tumors. Since it has achieved encouraging results in phase I studies against such tumors, phase II studies are now underway.…”

Section: Herpesvirus G207mentioning

confidence: 99%

The potential of oncolytic virus therapy for pancreatic cancer

et al. 2005

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The objective of this paper was to review a new category of gene therapy using oncolytic viruses for the treatment of pancreatic cancer. The eligibility and feasibility of oncolytic virus therapy as a novel therapeutic agent against pancreatic cancer are discussed as well as basic research for clinical trials, including a historical perspective and the current status of these novel agents. Even combination therapy, such as surgery with radiation and chemotherapy, has not significantly improved the survival rate of pancreatic cancer. Recently, a clinical trial (phase I and II) using an oncolytic adenovirus, ONYX-015, was completed in patients with pancreatic cancer. The phase II trial yielded beneficial results (tumor reduction or stabilization) in about 50% of the patients. A phase I study of the efficacy of oncolytic herpes viruses, G207, OncoVEX GM-CSF, and 1716 against a variety of tumors has been completed, and G207 is in phase II trials for use against brain tumors. In addition, a phase I trial using the herpesvirus showed good tolerance at all dosages. We discuss the basic scientific principles and current results of the above clinical trials with respect to these oncolytic viruses, and then compare the relative advantages and disadvantages of adenoviruses and herpesviruses as oncolytic agents. We also review the published literature on newly developed oncolytic viruses. The concept of oncolytic therapy has been studied for a century. Recent technological developments have made these oncolytic viruses more tumor-specific by exploiting the tumor cell environments. In addition, these viruses have been reported to increase the immunosusceptibility of the tumor cells, and have been designed to express other genes to increase the susceptibility of tumor cells to other therapeutic agents. Oncolytic virus therapy certainly appears to be a feasible treatment for pancreatic cancer.

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“…4 It contains deletions in both copies of the ICP34.5 gene, and an E. coli lacZ insertion that inactivates the ICP6 gene. African green monkey kidney cells ( Vero cells; ATCC, Rockville, MD ) were maintained in DMEM with 10% IFCS and penicillinstreptomycin.…”

Section: Virusmentioning

confidence: 99%

“…4 Due to these mutations, G207 replicates selectively within tumor cells and causes tumor cell destruction without local or systemic toxicity because its replication in normal cells is highly attenuated. G207 has been used as an antineoplastic agent for the treatment of brain tumors in both preclinical models and clinical trials.…”

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confidence: 99%

Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV

et al. 2002

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Here we developed an effective therapeutic approach using a replication -conditional mutant of herpes simplex virus ( HSV ), G207, for the treatment of metastatic tumors in the immunologically privileged central nervous system. An experimental model of brain metastasis was developed using BALB / c mice that harbored both intracranial ( i.c. ) and subcutaneous ( s.c. ) mouse CT26 colon adenocarcinoma tumors. Intratumoral injections of G207 into s.c. tumors elicited cytotoxic T -cell responses not only to HSV but also to a tumor antigen; however, only a limited antitumor effect was observed on metastatic brain tumors. To improve this antitumor effect, G207 was also injected into the brain tumor. After intratumoral injections of G207 into both i.c. and s.c. CT26 tumors, a significant antitumor effect was observed in the metastatic brain tumors. This therapeutic efficacy was absent in athymic mice, indicating that the antitumor effect could be mediated by T cells. Cytotoxic T -cell responses to HSV and the tumor antigen were induced by injections of G207 into i.c. and s.c. CT26 tumors. These results suggest that HSV -infected brain tumors may be efficiently eliminated by the induced anti -HSV T cells as well as by antitumor T cells. Therefore, this strategy of immuno -viral therapy, involving direct viral oncolytic activities and inducing antitumor and antiviral immune responses, may be useful for the treatment of tumors in the immunologically privileged central nervous system.

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Attenuated multi–mutated herpes simplex virus–1 for the treatment of malignant gliomas

Cited by 746 publications

References 29 publications

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties

The potential of oncolytic virus therapy for pancreatic cancer

Immuno-viral therapy of brain tumors by combination of viral therapy with cancer vaccination using a replication-conditional HSV

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