Comprehensive Development Program of Hunter-Killer Peptides for Prostate Cancer
Abstract
Previously, the authors invented Hunter Killer Peptides (HKP) for cancer therapy. In this comprehensive program to develop HKPs for prostate cancer, the authors accomplished the following: (1) evaluated an original HKP in the TRAMP mouse model of prostate cancer, showing that they could inhibit metastasis and demonstrating a trend toward extension of survival; (2) designed new peptides (both targeting and cell killing) and determined using in vitro assays that some of these new designs were superior (had improved therapeutic indices) to the original designs; (3) evaluated one of their most unique peptides (KP-5) in a PC-3 xenograft mouse model of prostate cancer, showing that they could limit primary tumor growth and increase survival; (4) determined that the dimeric form of one of their targeting peptides (HP-3) not only bound to aminopeptidase N (facilitating the internalization of HKPs into the cytosol of targeted endothelial cells to exert their anti-angiogenic effect), but also inhibited the enzymatic activity of aminopeptidase N, (also an anti-angiogenic effect) thus providing a synergetic anti-cancer effect; (5) determined that the dimeric form of one of their original HKPs (HKP-3) was more efficacious than the monomeric HKP-1; and (6) determined the LD50 of the original HKPs.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2005
- Accession Number
- ADA491213
Entities
People
- Howard M. Ellerby
Organizations
- Buck Institute for Research on Aging