Adenoviral-mediated gene transfer of interleukin-2 in a human breast cancer cell line and a fresh primary breast cancer culture

Neal W. Wilkinson, David M. Euhus

Research output: Contribution to journalArticle

Abstract

Adenovirally-mediated cytokine gene transfer has proven safe in the treatment of metastatic breast cancer. Unfortunately, the optimal conditions for gene transfer in the human breast remain largely unknown. Viral-mediated gene transfer was studied in a human breast cancer cell line and a fresh primary breast cancer culture using a type five adenoviral vector (AD5) containing the human interleukin 2 (IL-2) gene driven by a cytomegalovirus (CMV) promoter (AD5.CMV-IL2). IL-2 production was measured using an enzyme-linked immunosorbent assay (ELISA). In the human breast cancer cell line (MCF-7), IL-2 production increased logarithmically with viral dose and demonstrated peak production at 2000 ng/106 cells/24 h using a multiplicity of infection (MOI) of 3000:1. Transduction at a higher MOI resulted in cell death. IL-2 concentration reached over 2000 ng/ml 2 days after transduction and peaked 13 days after transduction at 5700 ng/ml. IL-2 levels declined thereafter. A fresh primary breast cancer culture, transduced with Ad5.CMV-IL2 at an MOI of 1000:1, secreted IL-2 at 15 ng/24 h 1 day after transduction and peaked at 85 ng/24 h 5 days after transduction. Adenoviral-mediated gene transfer was accomplished in breast cancer cells with high efficiency across a wide range of conditions. The optimal IL-2 dose required to maximally stimulate the immune system remains unknown.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalJournal of Investigative Surgery
Volume16
Issue number4
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Adenovirus
  • Breast cancer
  • Cytokine
  • Gene therapy
  • Gene transfer
  • Interleukin-2

ASJC Scopus subject areas

  • Surgery

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