Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase

Zhuangwu Li, Naga Shanmugam, Dai Katayose, Brian Huber, Shiv Srivastava, Kenneth H Cowan, Prem Seth

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231 -derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection of 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible.

Original languageEnglish (US)
Pages (from-to)113-117
Number of pages5
JournalCancer Gene Therapy
Volume4
Issue number2
StatePublished - Dec 1 1997

Fingerprint

Cytosine Deaminase
Prodrugs
Adenoviridae
Genetic Therapy
Flucytosine
Breast Neoplasms
Escherichia coli
Enzymes
Bystander Effect
Intraperitoneal Injections
Heterografts
Nude Mice
Neoplasms
Breast
Cell Line
Injections
Growth
Infection
Population

Keywords

  • 5-fluorocytosine
  • 5-fluorouracil
  • Cancer
  • Gene transfer
  • Nonmammalian enzyme
  • Suicide gene
  • Viral vectors

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase. / Li, Zhuangwu; Shanmugam, Naga; Katayose, Dai; Huber, Brian; Srivastava, Shiv; Cowan, Kenneth H; Seth, Prem.

In: Cancer Gene Therapy, Vol. 4, No. 2, 01.12.1997, p. 113-117.

Research output: Contribution to journalArticle

Li, Zhuangwu ; Shanmugam, Naga ; Katayose, Dai ; Huber, Brian ; Srivastava, Shiv ; Cowan, Kenneth H ; Seth, Prem. / Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase. In: Cancer Gene Therapy. 1997 ; Vol. 4, No. 2. pp. 113-117.
@article{63b181501d5e4b5ea76f71c53fce3a2f,
title = "Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase",
abstract = "A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10{\%} of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231 -derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection of 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible.",
keywords = "5-fluorocytosine, 5-fluorouracil, Cancer, Gene transfer, Nonmammalian enzyme, Suicide gene, Viral vectors",
author = "Zhuangwu Li and Naga Shanmugam and Dai Katayose and Brian Huber and Shiv Srivastava and Cowan, {Kenneth H} and Prem Seth",
year = "1997",
month = "12",
day = "1",
language = "English (US)",
volume = "4",
pages = "113--117",
journal = "Cancer Gene Therapy",
issn = "0929-1903",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Enzyme/prodrug gene therapy approach for breast cancer using a recombinant adenovirus expressing Escherichia coli cytosine deaminase

AU - Li, Zhuangwu

AU - Shanmugam, Naga

AU - Katayose, Dai

AU - Huber, Brian

AU - Srivastava, Shiv

AU - Cowan, Kenneth H

AU - Seth, Prem

PY - 1997/12/1

Y1 - 1997/12/1

N2 - A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231 -derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection of 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible.

AB - A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 cells infected with AdCD were 1000-fold more sensitive to 5-fluorocytosine (5-FC) than cells infected with a control adenovirus. Cell mixing experiments indicated that only 10% of AdCD-infected cells in a population were needed to induce complete cytotoxicity of noninfectious cells exposed to 5-FC. This suggests that bystander effects play an important role in AdCD-mediated cytotoxicities. Direct injection of AdCD into human breast MDA-MB-231 -derived tumors grown as xenografts in nude mice, followed by daily intraperitoneal injection of 5-FC was sufficient to inhibit tumor growth. These results suggest that in vivo gene therapy for breast cancer using AdCD is feasible.

KW - 5-fluorocytosine

KW - 5-fluorouracil

KW - Cancer

KW - Gene transfer

KW - Nonmammalian enzyme

KW - Suicide gene

KW - Viral vectors

UR - http://www.scopus.com/inward/record.url?scp=0031087212&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031087212&partnerID=8YFLogxK

M3 - Article

VL - 4

SP - 113

EP - 117

JO - Cancer Gene Therapy

JF - Cancer Gene Therapy

SN - 0929-1903

IS - 2

ER -