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 language | English (US) |
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Pages (from-to) | 203-208 |
Number of pages | 6 |
Journal | Journal of Investigative Surgery |
Volume | 16 |
Issue number | 4 |
DOIs | |
State | Published - Jan 1 2003 |
Externally published | Yes |
Keywords
- Adenovirus
- Breast cancer
- Cytokine
- Gene therapy
- Gene transfer
- Interleukin-2
ASJC Scopus subject areas
- Surgery