Episome-Based Gene Therapy Strategy for Treatment of Human Breast Cancer
Abstract
We have focussed our efforts on investigating the mechanisms by which antisense to type I insulin-like growth factor receptor (IGF-IR) or antisense to transforming growth factor beta (TGFbeta) reduces tumorigenicity in human and murine breast cancer cells. MDA-MB-435S human breast cancer cells expressing antisense IGF-IR enhanced apoptosis in vitro, which could contribute to the reduced tumorigenicity observed in vivo. A dramatic reduction in tumorigenesis and an absence of lung metastasis was seen in 3 models of immune compromised mice (nude, scid, scid-beige) injected with antisense IGF-IR transfected MDA-MB-435S cells. All mice injected with parental or control transfected cells developed large tumors. However, only the scid beige animals consistently exhibited pulmonary metastases indicating that this animal is the most suitable for studying the metastatic behavior of these human breast cancer cells. We have established baseline parameters for IL-2, IL-4, IL-5 and interferon gamma in EMT6 murine breast cancer cells and in antisense IGF-IR and antisense TGFbeta transfectants. Spleen cells from syngeneic mice injected with EMT6 cells expressing antisense TGF-beta show increased cytotoxicity. The percentage of apoptotic cells from tumors excised from these animals is significantly reduced.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1998
- Accession Number
- ADA345327
Entities
People
- Judith Ilan
Organizations
- Case Western Reserve University