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.