Breast Carcinoma Cell Targeted Therapy by Novel Vitamin D Analog
Abstract
Vitamin D and its analogs are growth-suppressing and cell-differentiating but also have high calcemic activity. We identified a new synthetic vitamin D analog: 1 alpha (OH)D5. In malignant breast cells, it induced expression of differentiation markers, namely alpha 2 integrin intracellular lipid and casein. Human breast carcinoma cells treated in vitro with 1 alpha (OH)D5 failed to form tumor when injected into athymic mice. In vivo, in athymic mice, dietary supplementation of 1 alpha (OH)D5 inhibited tumor growth and appeared to induce differentiation of transplanted human breast carcinoma cells. Animals receiving dietary 1 alpha (OH)D5 showed no serious deleterious effects except slight but significant increases in serum calcium. Serum calcium levels declined to that of control baseline level within one week of discontinuation of the treatment. We conjugated 1 alpha (OH)D5 with Her-2 antibody and evaluated its therapeutic efficacy in an experimental animal model. The 1 alpha (OH)D5-Her-2 conjugate inhibited the in vivo growth of breast carcinoma cells transplanted into athymic mice. The immunoconjugate was more effective than either agent administered alone in inhibiting growth of breast cancer cells. Animals receiving immunoconjugate showed no signs of toxicity or hypercalcemia.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA391706
Entities
People
- Rajeshwari R. Mehta
Organizations
- University of Illinois at Chicago