Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Thomann, S; Longerich, T; Bazhin, AV; Mier, W; Schemmer, P; Ryschich, E.
Selective targeting of liver cancer with the endothelial marker CD146.
Oncotarget. 2014; 5(18):8614-8624
Doi: 10.18632/oncotarget.2345
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Web of Science
PubMed
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- Co-authors Med Uni Graz
- Schemmer Peter
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- Abstract:
- Hepatocellular carcinomas are well-vascularized tumors; the endothelial cells in these tumors have a specific phenotype. Our aim was to develop a new approach for tumor-specific drug delivery with monoclonal antibody targeting of endothelial ligands. CD146, a molecule expressed on the endothelial surface of hepatocellular carcinoma, was identified as a promising candidate for targeting. In the present study, endothelial cells immediately captured circulating anti-CD146 (ME-9F1) antibody, while antibody binding in tumors was significantly higher than in hepatic endothelium. Macroscopically, after intravenous injection, there were no differences in the mean accumulation of anti-CD146 antibody in tumor compared to liver tissue , due to a compensating higher blood vessel density in the liver tissue. Additional blockade of nontumoral epitopes and intra-arterial administration, improved selective antibody capture in the tumor microvasculature and largely prevented antibody distribution in the lung and liver. The potential practical use of this approach was demonstrated by imaging of radionuclide-labeled ME-9F1 antibody, which showed excellent tumor-selective uptake. Our results provide a promising principle for the use of endothelial markers for intratumoral drug delivery. Tumor endothelium-based access might offer new opportunities for the imaging and therapy of hepatocellular carcinoma and other liver malignancies.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antibodies, Monoclonal - administration & dosage
- Antibodies, Monoclonal - metabolism
- Antibodies, Monoclonal - pharmacokinetics
- Antibody Specificity -
- Antigens, CD146 - immunology
- Antigens, CD146 - metabolism
- Biological Availability -
- Carcinoma, Hepatocellular - blood supply
- Carcinoma, Hepatocellular - drug therapy
- Carcinoma, Hepatocellular - immunology
- Carcinoma, Hepatocellular - metabolism
- Carcinoma, Hepatocellular - pathology
- Cell Line, Tumor -
- Drug Carriers -
- Endothelial Cells - immunology
- Endothelial Cells - metabolism
- Endothelial Cells - pathology
- Epitopes -
- Humans -
- Injections, Intravenous -
- Liver Circulation -
- Liver Neoplasms - blood supply
- Liver Neoplasms - drug therapy
- Liver Neoplasms - immunology
- Liver Neoplasms - metabolism
- Liver Neoplasms - pathology
- Mice, Inbred C3H -
- Mice, Inbred C57BL -
- Microcirculation -
- Find related publications in this database (Keywords)
- hepatocellular cancer
- drug delivery
- tumor endothelium