Endothelial Cell-Based Gene Therapy of Breast Cancer
Abstract
Recurrence and metastatic dissemination of breast cancers account for a significant morbidity and mortality in women, and effective means of treating this subset of patients remain elusive. The reports that intravenously (IV)-administered, genetically modified endothelial cells (GMBC) can target and incorporate into sites of active angiogenesis suggest that this strategy may be useful for the treatment of metastatic breast cancer. We evaluated whether IV-injected, interleukin (IL)-2 or IL12 gene-modified murine microvascular endothelial cells (IL-2/GMBC) can target sites of metastatic breast cancer, and whether the expression of hIL-2 or mIL- 12 transgene at the local tumor site can induce an anti-tumor immune response. Systemic administration of hIL-2/GMEC mediated significant reduction in the tumor burden of breast cancer and prolonged the survival of tumor-bearing mice. Immunocytochemical analysis of explanted tumors demonstrated presence of immune effectors (granulocytes, macrophages, CD4+ and CD8+ lymphocytes) within and around rhIL-2 positive tumors. Mice, which received only the hIL-2/GMEC without tumor cells, did not develop tumors and remained alive and well. Initial studies of tumor-bearing mice treated with IL-i 2/GMEC also show promising results. These findings suggest that systemic administration of GMEC is a potentially effective and safe strategy to target and treat metastatic breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADA408714
Entities
People
- John O. Ojeifo
Organizations
- Georgetown University