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MAbSilico: Informatics tools to characterise and design antibodies

The informatics tools developed by INRA and operated by the start-up MAbSilico make it possible to determine the epitope recognised by an antibody and to deduce potential cross reactions with other molecules. This represents a source of considerable savings for the human and veterinary health industries.

q14-a-infectiologie
Updated on 11/22/2018
Published on 09/25/2018

Antibodies: immense therapeutic potential, but their development remains highly empirical

Antibodies – and principally monoclonal antibodies – today represent a major source of innovation for new human or animal drugs.  Until now, the great majority of antibodies resulted from the immunisation of animals with chosen therapeutic targets, sometimes modified using empirical methods to enhance their efficacy. Because of this trial and error method, many of the antibodies thus developed subsequently failed during clinical trials because of a lack of efficacy. These failures are costly to industry and few alternative methods are currently available.

The in silico simulation of antigen-antibody interactions: INRA know-how

For many years now, scientists in the Joint Research Unit for Reproductive and Behavioural Physiology have been focusing on the potential of antibodies. In the field of animal reproduction, they may represent an alternative to hormones to control the reproduction of farmed livestock, notably by controlling LH and FSH receptors. For several years, the Biology and Bioinformatics of Signalling Systems team (Bios) has been developing algorithms to enabled detailed study of the protein-protein interactions that underpin the affinities of an antibody for its antigen. This research is now proving to be of particular interest to the human and veterinary pharmaceutical industries.

New tools to characterise antibodies

In the context of the MAbImprove LabEx, three additional and patented tools have been created to evaluate antibodies before in vivo testing:

  • MAbTope™: determination of epitopes* recognised by an antibody. This tool uses a specific algorithm to analyse the 3D structures of the antibody and antigen and to determine the epitope. This method is coupled with an in vitro validation step.
  • MabCross™: identification of crossed recognition with antibodies. Based on analysing the similarities of sequences and structures in epitope recognition regions (CDR, or Complementarity Determining Regions) between known antibodies and a new antibody, this tool identifies any cross-recognition between an antibody and proteins other than that targeted (“off target” effect). The consequences of such crossed recognitions may be positive or negative, but it is essential to determine them prior to any clinical trials.
  • MAbSubstitute™: in silico identification of alternatives to a determined antibody. This tool compares the CDR of an antibody (sequence and structure) with those available in a database. Antibodies with a similar CDR may bind to the same target molecule.

Tools exploited by a start-up

These results are now being exploited (licence on the patents) by MAbSilico, a start-up created at INRA. There is currently no other company in this market with skills and services which can match those offered by MAbSilico.
Developments are anticipated that will continue to refine the existing tools. The scientists are currently working on developing an informatics tool that would enable the de novo design of antibodies specific to a given target.  This would enable considerable savings in time when creating an antibody, as well as markedly reducing any adverse effects.
*Epitope: a specific part of an antigen that is recognised by an antibody

Contact(s)
Scientific contact(s):

  • Anne POUPON CNRS–IFCE-INRA-Université de Tours Joint Research Unit for Reproductive and Behavioural Physiology (UMR PRC) (Biology and Bioinformatics of Signalling Systems team; BIOS 37380 Nouzilly, FRANCE
  • Pascale CREPIEUX CNRS–IFCE-INRA-Université de Tours Joint Research Unit for Reproductive and Behavioural Physiology (UMR PRC) (Biology and Bioinformatics of Signalling Systems team; BIOS 37380 Nouzilly, FRANCE
Associated Division(s):
Animal Physiology and Livestock Systems
Associated Centre(s):
Val de Loire
MAbSilico

MAbSilico

MAbSilico is a start-up that was created in September 2017. It resulted from work by the BIOS team in the CNRS–IFCE-INRA-Université de Tours Joint Research Unit for Reproductive and Behavioural Physiology (UMR PRC).
MAbSilico can offer services regarding the characterisation of therapeutic antibodies during their early stages of development. It can identify the epitope of an antibody on its target (MAbTope™), evaluate any cross recognition of an antibody (MAbCross™) and determine alternatives to an antibody that has been identified but cannot be used (MAbSubstitute™). It uses in silico methods that are combined with experimentation.
MAbSilico is led by Vincent PUARD (President and co-founder) and Astrid MUSNIER (CEO and co-founder). The company is hosted on the INRA campus in Nouzilly.

Contacts:
Vincent PUARD
Astrid MUSNIER


https://www.mabsilico.com

LabEx MAbImprove

Le LabEx MAbImprove

LThe purpose of the MAbImprove Laboratory of Excellence (LabEx) is to develop new methods to obtain antibodies. Based on a partnership between the Universities of Tours and Montpellier, associating INSERM, CNRS, INRA, Tours University Hospital and the Montpellier Cancer Institute (ICM), MAbImprove federates 19 research teams and more than 200 scientists. It is based on the complementarity of its two sites, as much as on a national network of academic teams involved in the project, and the numerous pharmaceutical and biotechnology firms that are directly interested in its outcomes.

Driven by the Léonard de Vinci COMUE (Community of Universities and Establishments), the MAbImprove project was accredited as a Laboratory of Excellence on 25 March 2011, with funding from the French government’s Investments for the Future programme (PIA) worth €8 million over 10 years. MAbImprove is led by Prof Hervé Watier (coordinator, Tours) and Dr André Pèlegrin (deputy coordinator, Montpellier).

For more information: http://mabimprove.univ-tours.fr/fr/

For more information

Patent: WO2018087494 “Method for predicting the cross-recognition of targets by different antibodies”
Bibliography:

  • Bourquard T., et al.. (2015). Unraveling the molecular architecture of a G protein-coupled receptor/ β-arrestin/ Erk module complex. Sci. Rep., 5, 10760.
  • Bourquard T., et al.(2018). MAbTope, fast and robust epitope mapping method. J. Immunol., en révision