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Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy

Marie Godar UGent, Virginia Morello, Ava Sadi, Anna Hultberg, Natalie De Jonge, Cristina Basilico, Valérie Hanssens, Michael Saunders, Bart Lambrecht UGent, Mohamed El Khattabi, et al. (2016) SCIENTIFIC REPORTS. 6.
abstract
Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IGG ANTIBODIES, CHAIN ASSOCIATION, GROWTH-FACTOR, TUMOR-CELLS, T-CELLS, FRAGMENTS, CANCER, CHROMATOGRAPHY, BISPECIFIC ANTIBODIES, SINGLE-DOMAIN ANTIBODY
journal title
SCIENTIFIC REPORTS
Sci. Rep.
volume
6
article number
31621
pages
12 pages
Web of Science type
Article
Web of Science id
000381700900001
JCR category
MULTIDISCIPLINARY SCIENCES
JCR impact factor
4.259 (2016)
JCR rank
10/64 (2016)
JCR quartile
1 (2016)
ISSN
2045-2322
DOI
10.1038/srep31621
language
English
UGent publication?
yes
classification
A1
copyright statement
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
id
8132438
handle
http://hdl.handle.net/1854/LU-8132438
date created
2016-11-03 14:20:01
date last changed
2017-07-04 08:51:51
@article{8132438,
  abstract     = {Bispecific antibodies are of great interest due to their ability to simultaneously bind and engage different antigens or epitopes. Nevertheless, it remains a challenge to assemble, produce and/or purify them. Here we present an innovative dual anti-idiotypic purification process, which provides pure bispecific antibodies with native immunoglobulin format. Using this approach, a biparatopic IgG1 antibody targeting two distinct, HGF-competing, non-overlapping epitopes on the extracellular region of the MET receptor, was purified with camelid single-domain antibody fragments that bind specifically to the correct heavy chain/light chain pairings of each arm. The purity and functionality of the anti-MET biparatopic antibody was then confirmed by mass spectrometry and binding experiments, demonstrating its ability to simultaneously target the two epitopes recognized by the parental monoclonal antibodies. The improved MET-inhibitory activity of the biparatopic antibody compared to the parental monoclonal antibodies, was finally corroborated in cell-based assays and more importantly in a tumor xenograft mouse model. In conclusion, this approach is fast and specific, broadly applicable and results in the isolation of a pure, novel and native-format anti-MET biparatopic antibody that shows superior biological activity over the parental monospecific antibodies both in vitro and in vivo.},
  articleno    = {31621},
  author       = {Godar, Marie and Morello, Virginia and Sadi, Ava and Hultberg, Anna and De Jonge, Natalie and Basilico, Cristina and Hanssens, Val{\'e}rie and Saunders, Michael and Lambrecht, Bart and El Khattabi, Mohamed and de Haard, Hans and Michieli, Paolo and Blanchetot, Christophe},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {IGG ANTIBODIES,CHAIN ASSOCIATION,GROWTH-FACTOR,TUMOR-CELLS,T-CELLS,FRAGMENTS,CANCER,CHROMATOGRAPHY,BISPECIFIC ANTIBODIES,SINGLE-DOMAIN ANTIBODY},
  language     = {eng},
  pages        = {12},
  title        = {Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy},
  url          = {http://dx.doi.org/10.1038/srep31621},
  volume       = {6},
  year         = {2016},
}

Chicago
Godar, Marie, Virginia Morello, Ava Sadi, Anna Hultberg, Natalie De Jonge, Cristina Basilico, Valérie Hanssens, et al. 2016. “Dual Anti-idiotypic Purification of a Novel, Native-format Biparatopic anti-MET Antibody with Improved in Vitro and in Vivo Efficacy.” Scientific Reports 6.
APA
Godar, M., Morello, V., Sadi, A., Hultberg, A., De Jonge, N., Basilico, C., Hanssens, V., et al. (2016). Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Godar M, Morello V, Sadi A, Hultberg A, De Jonge N, Basilico C, et al. Dual anti-idiotypic purification of a novel, native-format biparatopic anti-MET antibody with improved in vitro and in vivo efficacy. SCIENTIFIC REPORTS. 2016;6.
MLA
Godar, Marie, Virginia Morello, Ava Sadi, et al. “Dual Anti-idiotypic Purification of a Novel, Native-format Biparatopic anti-MET Antibody with Improved in Vitro and in Vivo Efficacy.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.