Breast Carcinoma Cell Targeted Therapy by Novel Vitamin D Analog
Abstract
Vitamin D and its analogs have growth-suppressing and cell-differentiating effects on various carcinoma cell types. We have synthesized a vitamin D analog (1 alpha(OH)D5) that is nontoxic and has both growth-inhibitory and cell-differentiating actions in various established breast cancer cell lines. Our original goal was to covalently link this vitamin D analog to antibody against Her-2/neu protein and thus deliver 1 alpha(OH)D5 specifically to highly aggressive human breast cancer cells. Using the xenograft model, we previously confirmed that 1 alpha(OH)D5 supplemented in the diet inhibits growth of human breast carcinoma cells transplanted into athymic mice. As a second phase of the study, we covalently linked lalpha(OH)D5 to Her-2/neu antibody using sulfo-SANPAR linker. The 1 alpha(OH)D5-Her-2 conjugate specifically binds to Her-2 receptor-expressing breast cancer cells. The conjugate was able to compete with unconjugated Her-2 antibody for Her-2 receptor binding sites on the cancer cells. Our preliminary results show that the conjugate, when injected into Her-2+ tumor- bearing athymic mice, shows significantly higher accumulation in tumor than in other visceral organs. Experiments are in progress to further characterize the properties of 1 alpha(OH)D5-Her-2 antibody immunoconjugate and its effect on in vivo growth of human breast carcinoma cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA381134
Entities
People
- Rajeshwari Mehta
Organizations
- University of Illinois at Chicago