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Effect of vitamin D analog (1alpha hydroxy D5) immunoconjugated to Her-2 antibody on breast cancer
Vasil Punj1, Jewell M Graves, Rajeshwari R Mehta
1Department of Surgical Oncology, University of Illinois at Chicago, 840 South Wood Street, M/C 820, Chicago, IL 60612, USA.
Abstract:
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.
Insights
Targeted delivery of vitamin D analog 1alpha(OH)D5 (D5) using Her-2 antibody conjugates significantly inhibited breast cancer growth. This immunoconjugation approach shows therapeutic potential for Her-2 positive breast cancer.
Area of Science:
- Oncology
- Endocrinology
- Immunology
Background:
- Vitamin D analog 1alpha(OH)D5 (D5) demonstrated efficacy in inhibiting breast cancer cell growth and inducing differentiation.
- Targeted drug delivery systems are crucial for enhancing therapeutic outcomes and minimizing side effects in cancer treatment.
Purpose of the Study:
- To investigate the therapeutic potential of specifically delivering D5 to breast cancer cells via conjugation with a Her-2 antibody.
- To evaluate the efficacy of the D5-Her-2 antibody conjugate (IMC) in inhibiting the growth of Her-2 positive breast cancer cells both in vitro and in vivo.
Main Methods:
- D5 was conjugated to a Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) linker to create an immunoconjugate (IMC).
- In vitro studies assessed IMC's binding specificity, receptor competition, and internalization in Her-2-expressing cells.
- In vivo efficacy was evaluated by transplanting BT-474 cells into athymic mice and administering IMC intraperitoneally weekly for 6 weeks.
Main Results:
- The IMC specifically bound to Her-2-expressing cells, competed with Her-2 antibody for the surface receptor, and induced internalization.
- IMC treatment significantly inhibited the growth of BT-474 cells transplanted into athymic mice.
- The in vivo growth inhibition achieved with IMC was comparable to continuous dietary supplementation with D5.
Conclusions:
- Targeted delivery of D5 via immunoconjugation to Her-2 antibodies offers a promising therapeutic strategy for Her-2 positive breast cancer.
- This approach demonstrates effective growth inhibition of breast cancer xenografts in vivo.
- Further development of D5-based immunoconjugates holds potential for improved breast cancer treatment.
