A New in Silico antibody similarity measure both identifies large sets of epitope binders with distinct CDRs and accurately predicts off-target reactivity - Archive ouverte HAL Access content directly
Journal Articles International Journal of Molecular Sciences Year : 2022

A New in Silico antibody similarity measure both identifies large sets of epitope binders with distinct CDRs and accurately predicts off-target reactivity

(1, 2) , (1, 2) , (2, 3) , (2) , (2) , (2) , (2) , (1) , (2) , (2) , (3) , (4) , (2, 5) , (2, 5) , (2, 5, 1)
1
2
3
4
5
Yannick Corde
  • Function : Author
Sandra Cortes
  • Function : Author

Abstract

Developing a therapeutic antibody is a long, tedious, and expensive process. Many obstacles need to be overcome, such as biophysical properties (issues of solubility, stability, weak production yields, etc.), as well as cross-reactivity and subsequent toxicity, which are major issues. No in silico method exists today to solve such issues. We hypothesized that if we were able to properly measure the similarity between the CDRs of antibodies (Ab) by considering not only their evolutionary proximity (sequence identity) but also their structural features, we would be able to identify families of Ab recognizing similar epitopes. As a consequence, Ab within the family would share the property to recognize their targets, which would allow (i) to identify off-targets and forecast the cross-reactions, and (ii) to identify new Ab specific for a given target. Testing our method on 238D2, an antagonistic anti-CXCR4 nanobody, we were able to find new nanobodies against CXCR4 and to identify influenza hemagglutinin as an off-target of 238D2.
Fichier principal
Vignette du fichier
ijms-23-09765-v2.pdf (4.96 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Licence : CC BY - Attribution

Dates and versions

hal-03838203 , version 1 (10-11-2022)

Licence

Attribution - CC BY 4.0

Identifiers

Cite

Astrid Musnier, Thomas Bourquard, Amandine Vallet, Laetitia Mathias, Gilles Bruneau, et al.. A New in Silico antibody similarity measure both identifies large sets of epitope binders with distinct CDRs and accurately predicts off-target reactivity. International Journal of Molecular Sciences, 2022, 23 (17), pp.1-17. ⟨10.3390/ijms23179765⟩. ⟨hal-03838203⟩
0 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More