Effect of vitamin D analog (1? hydroxy D5) immunoconjugated to Her-2 antibody on breast cancer
| Autor: | J. M. Graves, Vasil Punj, Rajeshwari R. Mehta |
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| Rok vydání: | 2004 |
| Předmět: |
Azides
Cytoplasm Cancer Research medicine.medical_specialty Time Factors Mammary gland Mice Nude Succinimides Breast Neoplasms Biology Pharmacology Mice Breast cancer Antigens Neoplasm Cell surface receptor In vivo Cell Line Tumor Internal medicine medicine Animals Vitamin D Receptor Dose-Response Relationship Drug Hydroxycholecalciferols Cell Membrane Temperature Caseins Cell Differentiation Genes erbB-2 Lipid Metabolism medicine.disease In vitro Immunoconjugate Ki-67 Antigen medicine.anatomical_structure Endocrinology Oncology biology.protein Calcium Female Antibody Cell Division Protein Binding |
| Zdroj: | International Journal of Cancer. 108:922-929 |
| ISSN: | 1097-0215 0020-7136 |
| DOI: | 10.1002/ijc.11590 |
| Popis: | We previously showed that a new vitamin D analog, 1α(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 μg 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. © 2003 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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