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TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery

TriFabs are IgG-shaped bispecific antibodies (bsAbs) composed of two regular Fab arms fused via flexible linker peptides to one asymmetric third Fab-sized binding module. This third module replaces the IgG Fc region and is composed of the variable region of the heavy chain (VH) fused to CH3 with “kn...

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Autores principales: Mayer, Klaus, Baumann, Anna-Lena, Grote, Michael, Seeber, Stefan, Kettenberger, Hubert, Breuer, Sebastian, Killian, Tobias, Schäfer, Wolfgang, Brinkmann, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661895/
https://www.ncbi.nlm.nih.gov/pubmed/26593903
http://dx.doi.org/10.3390/ijms161126037
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author Mayer, Klaus
Baumann, Anna-Lena
Grote, Michael
Seeber, Stefan
Kettenberger, Hubert
Breuer, Sebastian
Killian, Tobias
Schäfer, Wolfgang
Brinkmann, Ulrich
author_facet Mayer, Klaus
Baumann, Anna-Lena
Grote, Michael
Seeber, Stefan
Kettenberger, Hubert
Breuer, Sebastian
Killian, Tobias
Schäfer, Wolfgang
Brinkmann, Ulrich
author_sort Mayer, Klaus
collection PubMed
description TriFabs are IgG-shaped bispecific antibodies (bsAbs) composed of two regular Fab arms fused via flexible linker peptides to one asymmetric third Fab-sized binding module. This third module replaces the IgG Fc region and is composed of the variable region of the heavy chain (VH) fused to CH3 with “knob”-mutations, and the variable region of the light chain (VL) fused to CH3 with matching “holes”. The hinge region does not contain disulfides to facilitate antigen access to the third binding site. To compensate for the loss of hinge-disulfides between heavy chains, CH3 knob-hole heterodimers are linked by S354C-Y349C disulphides, and VH and VL of the stem region may be linked via VH44C-VL100C disulphides. TriFabs which bind one antigen bivalent in the same manner as IgGs and the second antigen monovalent “in between” these Fabs can be applied to simultaneously engage two antigens, or for targeted delivery of small and large (fluorescent or cytotoxic) payloads.
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spelling pubmed-46618952015-12-10 TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery Mayer, Klaus Baumann, Anna-Lena Grote, Michael Seeber, Stefan Kettenberger, Hubert Breuer, Sebastian Killian, Tobias Schäfer, Wolfgang Brinkmann, Ulrich Int J Mol Sci Article TriFabs are IgG-shaped bispecific antibodies (bsAbs) composed of two regular Fab arms fused via flexible linker peptides to one asymmetric third Fab-sized binding module. This third module replaces the IgG Fc region and is composed of the variable region of the heavy chain (VH) fused to CH3 with “knob”-mutations, and the variable region of the light chain (VL) fused to CH3 with matching “holes”. The hinge region does not contain disulfides to facilitate antigen access to the third binding site. To compensate for the loss of hinge-disulfides between heavy chains, CH3 knob-hole heterodimers are linked by S354C-Y349C disulphides, and VH and VL of the stem region may be linked via VH44C-VL100C disulphides. TriFabs which bind one antigen bivalent in the same manner as IgGs and the second antigen monovalent “in between” these Fabs can be applied to simultaneously engage two antigens, or for targeted delivery of small and large (fluorescent or cytotoxic) payloads. MDPI 2015-11-17 /pmc/articles/PMC4661895/ /pubmed/26593903 http://dx.doi.org/10.3390/ijms161126037 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mayer, Klaus
Baumann, Anna-Lena
Grote, Michael
Seeber, Stefan
Kettenberger, Hubert
Breuer, Sebastian
Killian, Tobias
Schäfer, Wolfgang
Brinkmann, Ulrich
TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery
title TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery
title_full TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery
title_fullStr TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery
title_full_unstemmed TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery
title_short TriFabs—Trivalent IgG-Shaped Bispecific Antibody Derivatives: Design, Generation, Characterization and Application for Targeted Payload Delivery
title_sort trifabs—trivalent igg-shaped bispecific antibody derivatives: design, generation, characterization and application for targeted payload delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4661895/
https://www.ncbi.nlm.nih.gov/pubmed/26593903
http://dx.doi.org/10.3390/ijms161126037
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