[Targeting--a new way to identify unknown tumor markers in blood vessels].
The expression of specific molecules on the surface of vascular endothelial cells in tumours might be a key to anticancer therapy with angiostatic drugs. A new method to find these molecules on tumour vessels, targeting, is presented here. Some of these tumour-specific molecules have been identified by means of so called phage libraries. They are gene-manipulated phages, where the surface is decorated with randomly generated short peptides. After intravenous injection a few of the peptides, expressed on the surface of the phage, attach to complementary structures on the endothelial cell, as a ligand attaches to its receptor. Through biopsies and immunohistochemistry the phage can be isolated and identified. The part of the DNA of the phage that codes for the peptide-sequence of importance is sequenced. This seeking for such vessel-addresses can in the future be used for diagnostic purposes and also for local tumour-treatment. It is envisioned that cytotoxic drugs can be coupled to peptides on nanoparticles and act locally, in order to minimize toxic systemic side effects.
Wallin
Emelie
E
Karolinska institutet, Stockholm, Sweden.
Akerman
Maria E
ME
Palmblad
Jan
J
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D004730:Endothelium, Vascular / Q000378:metabolism*; D000077270:Exenatide; D005934:Glucagon / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D000069450:Liraglutide; D049329:Nanostructures; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019151:Peptide Library; D010455:Peptides / Q000627:therapeutic use; D011498:Protein Precursors / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors; D014688:Venoms / Q000627:therapeutic use
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D019151:Peptide Library; D010455:Peptides; D011498:Protein Precursors; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077270:Exenatide; C415802:DP IV-related protease, human; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases