title: 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.affiliation: National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
authors.forename: Fatemeh Rahimi
authors.initials: FR
authors.lastname: Jamnani
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Rahbarizadeh
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Shokrgozar
authors.forename: Davoud
authors.initials: D
authors.lastname: Ahmadvand
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Mahboudi
authors.forename: Zahra
authors.initials: Z
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry; D000915:Antibody Affinity; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000737:chemistry; D001667:Binding, Competitive; D002162:Camelus; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007128:Immunoglobulin Fragments / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D051379:Mice; D019151:Peptide Library; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000939:Epitopes; D007128:Immunoglobulin Fragments; D007143:Immunoglobulin Heavy Chains; D019151:Peptide Library; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D000068878:Trastuzumab; C508053:ERBB2 protein, human