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Phage-displayed random peptide libraries in mice: toxicity after serial panning
David N Krag1, Susan P Fuller, Lyn Oligino
1Department of Surgery, College of Medicine and the Vermont Comprehensive Cancer Center, Given Bldg Rm E309, Burlington, VT 05405, USA. David.Krag@uvm.edu
Cancer Chemotherapy and Pharmacology
|October 3, 2002
Summary
This study developed a safe in vivo phage-displayed random peptide library (RPL) screening method for cancer research. The technique allows serial panning in individual mice, leading to consensus sequences and paving the way for human clinical trials.
Area of Science:
- Biotechnology
- Molecular Biology
- Oncology
Background:
- Phage-displayed random peptide libraries (RPLs) identify ligands for specific cell targets.
- Previous in vivo screening methods caused harm to animals.
- Targeting tumor vasculature with peptides has shown promise in eradicating tumors.
Purpose of the Study:
- To develop a non-harmful in vivo RPL screening process for identifying peptide ligands.
- To establish a method for serial panning within individual animals for cancer therapy development.
Main Methods:
- RPLs were administered to mice in various dosing formats.
- Phage were amplified from excised tumor nodules after 10 minutes.
- Serial re-injection and panning were performed up to three times in the same animal.
- Mice were monitored for toxicity and organ phage presence.
Main Results:
- Administration of RPLs showed minimal toxicity in mice.
- Consensus amino acid sequences were identified.
- Some identified sequences showed similarity to peptide ligands targeting matrix metalloproteinases.
Conclusions:
- Serial administration of RPLs is well-tolerated in mice.
- Serial panning in individual mice is feasible for identifying consensus sequence motifs.
- Preclinical data support the initiation of human clinical trials.