Targeting high affinity and epitope-distinct oligoclonal nanobodies to HER2 over-expressing tumor cells.

Abstract

Modern anti-HER2 antibody therapy tends to exploit a panel of different antibodies against different epitopes on the antigen. For this aim, nanobodies are very striking targeting agents and can be easily produced against any cell-specific membrane antigen. The oligoclonal nanobodies can be used to block more than one functional epitope on a target antigen and inhibit the generation of escape variants associated with cancer therapy. In this study, 12 nanobody clones selected from an immune camel library were examined for their ability to differ between tumor markers. These oligoclonal nanobodies targeted breast cancer cells better than each individual nanobody. In epitope mapping, several nanobodies overlapped in the epitope recognized by trastuzumab and some of the non-overlapping nanobodies could affect the binding of trastuzumab to HER2. This study demonstrates that the oligoclonal nanobodies are potential therapeutic tools that can be used instead of, or in combination with trastuzumab to assess tumor viability during treatment.

• Authors: Fatemeh Rahimi Jamnani, Fatemeh Rahbarizadeh, Mohammad A Shokrgozar, Davoud Ahmadvand, Fereidoun Mahboudi, Zahra Sharifzadeh
• Journal: Experimental cell research (Exp Cell Res) Vol. 318 Issue 10 Pg. 1112-24 (Jun 10 2012) ISSN: 1090-2422 [Electronic] United States
• PMID: 22440788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• Epitopes
• Immunoglobulin Fragments
• Immunoglobulin Heavy Chains
• Peptide Library
• Recombinant Proteins
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Animals
• Antibodies, Monoclonal, Humanized (chemistry)
• Antibody Affinity
• Antibody Specificity
• Antineoplastic Agents (chemistry)
• Binding, Competitive
• Camelus
• Cell Line, Tumor
• Enzyme-Linked Immunosorbent Assay
• Epitopes (chemistry, immunology)
• Flow Cytometry
• Humans
• Immunoglobulin Fragments (biosynthesis, chemistry, isolation & purification)
• Immunoglobulin Heavy Chains (biosynthesis, chemistry, isolation & purification)
• Mice
• Peptide Library
• Protein Binding
• Receptor, ErbB-2 (chemistry, immunology, metabolism)
• Recombinant Proteins (biosynthesis, isolation & purification)
• Trastuzumab