The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors

Samita Andreansky, Bin He, G. Yancey Gillespie, Liliana Soroceanu, James Markert, Joany Chou, Bernard Roizman, Richard J. Whitley

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with γ134.5 mutants, R3616 (from which both copies of the γ134.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the γ134.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate γ134.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the γ134.5 gene has been replaced by the murine homologue, MyD116, are considered.

Original languageEnglish
Pages (from-to)11313-11318
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
StatePublished - Oct 15 1996
Externally publishedYes

Fingerprint

Simplexvirus
Brain Neoplasms
Glioma
Viruses
HhAntag691
Genes
Neoplasms
Survival
Terminator Codon
Therapeutics

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. / Andreansky, Samita; He, Bin; Gillespie, G. Yancey; Soroceanu, Liliana; Markert, James; Chou, Joany; Roizman, Bernard; Whitley, Richard J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 21, 15.10.1996, p. 11313-11318.

Research output: Contribution to journalArticle

Andreansky, Samita ; He, Bin ; Gillespie, G. Yancey ; Soroceanu, Liliana ; Markert, James ; Chou, Joany ; Roizman, Bernard ; Whitley, Richard J. / The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 21. pp. 11313-11318.
@article{15be583e86e543a484617de2c938675c,
title = "The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors",
abstract = "Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with γ134.5 mutants, R3616 (from which both copies of the γ134.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the γ134.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate γ134.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the γ134.5 gene has been replaced by the murine homologue, MyD116, are considered.",
author = "Samita Andreansky and Bin He and Gillespie, {G. Yancey} and Liliana Soroceanu and James Markert and Joany Chou and Bernard Roizman and Whitley, {Richard J.}",
year = "1996",
month = "10",
day = "15",
doi = "10.1073/pnas.93.21.11313",
language = "English",
volume = "93",
pages = "11313--11318",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "21",

}

TY - JOUR

T1 - The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors

AU - Andreansky, Samita

AU - He, Bin

AU - Gillespie, G. Yancey

AU - Soroceanu, Liliana

AU - Markert, James

AU - Chou, Joany

AU - Roizman, Bernard

AU - Whitley, Richard J.

PY - 1996/10/15

Y1 - 1996/10/15

N2 - Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with γ134.5 mutants, R3616 (from which both copies of the γ134.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the γ134.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate γ134.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the γ134.5 gene has been replaced by the murine homologue, MyD116, are considered.

AB - Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with γ134.5 mutants, R3616 (from which both copies of the γ134.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the γ134.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate γ134.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the γ134.5 gene has been replaced by the murine homologue, MyD116, are considered.

UR - http://www.scopus.com/inward/record.url?scp=0029961357&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029961357&partnerID=8YFLogxK

U2 - 10.1073/pnas.93.21.11313

DO - 10.1073/pnas.93.21.11313

M3 - Article

VL - 93

SP - 11313

EP - 11318

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 21

ER -