Synthetic peptides (selectides) produced and screened in other components of this NCDDG will be selected based on their cytotoxic or cytostatic activity against 6 standardized human cell lines (HL60 leukemia, A375 melanoma, MCF-7 breast cancer, SW480 colon cancer, A549 lung cancer and NCap prostate cancer). These cell lines grow in a reproducible fashion with readily measured end points when implanted in the severe combined immune deficient (SCID) mouse. The SCID mouse implanted with these lines will be used to evaluate synthetic peptides with in vitro activity to determine their pharmacokinetics maximum tolerated dose and efficacy. SCID mice (15 animals per treatment group) will be inoculated with the cell type or types which showed sensitivity in vitro. On appearance of the first tumor, daily therapy with the selected peptide will be initiated and continued for 4 weeks. Subcutaneous tumor size will be compared to untreated animals. The dose and schedule of therapy will be determined by pharmacological and toxicological studies. Feedback of results to other projects will result in additional peptides, modified to improve their pharmacological or therapeutic profile. The anticipated outcome is the identification of peptides with antitumor activity to be submitted to the NCI and the Selectide Corporation for further development.
| Salmon, S E; Liu-Stevens, R H; Zhao, Y et al. (1996) High-volume cellular screening for anticancer agents with combinatorial chemical libraries: a new methodology. Mol Divers 2:57-63 |
| Nikolaiev, V; Stierandova, A; Krchnak, V et al. (1993) Peptide-encoding for structure determination of nonsequenceable polymers within libraries synthesized and tested on solid-phase supports. Pept Res 6:161-70 |
