Development of Ligand-Transformed Alpha-Fetoprotein for Use Against Breast Cancer in Humans
Abstract
The purpose of this study was to produce large quantities of the active form of alpha-fetoprotein (AFP) and assess its effectiveness in the control of estrogen-stimulated growth of experimental human breast cancers. Both recombinant and natural AFP were produced for this purpose. AFP stopped the estrogen-stimulated growth of MCF-7 and T47 human breast cancers and the MCF-10A human benign breast tumor grown as xenografts in immune-deficient mice. AFP did not interfere with the estrogen-independent growth of MDA-MB-231 and BT20 human breast cancer xenografts. Positivity for sex steroid hormone receptors was a marker of tumor sensitivity to the growth-inhibitory effects of AFP. Elevations in serum FSH and E2 were intermediate markers of AFP's biological activity. The histomorphometric profile of growth-inhibited tumors was one of cytostasis, not cytotoxicity, with cells accumulating in the (G0/G1 phase of the cell cycle. There was no evidence of toxicity associated with chronic treatment with AFP. The active site of this protein is an 8-amino-acid peptide located near the C-terminal part of the molecule. This peptide was synthesized in quantity and retained full biological activity. The peptide requires further study, since it is more clinically translatable as a pharmaceutical for the treatment of breast cancer than the full-length protein.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 1999
- Accession Number
- ADA371367
Entities
People
- James A. Bennett
Organizations
- Albany Medical College