sulfosuccinimidyl-6-((4-azido-2-nitrophenyl)amino)hexanoate and Breast-Neoplasms

We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell-differentiating action. In vitro, D5-Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2-expressing cells, to compete with Her-2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 microg Her-2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her-2 positive breast cancer.

Topics: Animals; Antigens, Neoplasm; Azides; Breast Neoplasms; Calcium; Caseins; Cell Differentiation; Cell Division; Cell Line, Tumor; Cell Membrane; Cytoplasm; Dose-Response Relationship, Drug; Female; Genes, erbB-2; Hydroxycholecalciferols; Ki-67 Antigen; Lipid Metabolism; Mice; Mice, Nude; Protein Binding; Succinimides; Temperature; Time Factors; Vitamin D