Targeted Tumor Therapy


Phage Selection Process

The process of finding homing peptides is a long, arduous, expensive process.  The above illustration schematically depicts the process in finding a peptide that can target a specific tissue.  The process was first developed to be used in vitro and then adapted for in vivo screening.  To start, a library of peptide-expressing phages must be created.  Oligonucleotide vectors are constructed and transformed into an E. coli culturePhage was extracted and screened for surface-peptide expression.  These phages can then be injected into the tail vein of rats.  Phages which express peptide that bind to a specific tissue, concentrate at that site.  Tissue is then harvested from the animal and is incubated with a fluorescently-tagged antibody specific for the phage.  This will then allow the scientist to visualize where the phage has localized.  Many times, the phage will not localize to a specific site and will not be useful for targeted therapy.  If a phage is found to localize at a specific site, the second step is to isolate the peptide which is responsible for the phage homing.  Uses DNA sequencing, the homing peptide is then isolated and can be mass produced.  Through this process, it has been revealed a strong heterogeneity amongst the vasculature of different tissues.  This has led to the theory that tumors can be specifically destroyed by targeting their vasculature.  The table below documents some of the peptides that have been isolated through this process and the tissue they specifically target.

Top illustration taken from Ruoslahti, Nature Reviews Cancer, 2002
Bottom table taken from Ruoslahti, Drug Discovery Today, 2002

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Website created by Suraj Kachgal
University of California, Irvine
BME 240
June 2006

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