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CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor

  • Philippe P. Pagni
  • Anitra Wolf
  • Mauro Lo Conte
  • Ronald Yeh
  • Guangsen Fu
  • Fa Liu
  • Matthias von Herrath
  • Ken CoppietersEmail author
Letter
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To the Editor: The CD40-CD40 ligand (CD40L, also known as CD154) pathway has been identified as a potential target for pharmaceutical intervention in type 1 diabetes [1, 2]. The CD40-targeted peptide approach published by Wagner and colleagues in Diabetologia in 2014 [3] captured our attention because their data indicated that the peptide used in their research induced potent diabetes prevention and possible diabetes reversal in the gold-standard NOD mouse model of type 1 diabetes. Moreover, in contrast to other anti-CD40L antibodies, it was suggested that the peptide format used in the paper by Wagner’s group [3] would not cause anti-CD40L immune complexes to trigger Fcγ type 2 receptor A (FcγRIIa) signalling through an Fc moiety, thus avoiding platelet activation and the subsequent thrombotic complications associated with these antibodies [4].

The in vivo data obtained by Wagner’s group [3] imply that the CD40L-derived 15-mer peptide would bind to CD40 with high enough affinity to...

Keywords

CD40 CD40L Type 1 diabetes 

Abbreviations

CD40L

CD40 ligand

SPR

Surface plasmon resonance

Notes

Contribution statement

PPP, AW, MLC, RY, GF and FL contributed to the conception and design, acquisition of data, or analysis and interpretation of data. MvH and KC contributed to the conception and design and interpretation of data. All authors contributed to drafting the article or revising it critically for important intellectual content and approved of the version to be published. KC is responsible for the integrity of the work as a whole.

Funding

All authors performed this work while under employment of Novo Nordisk.

Duality of interest

The authors declare employment at Novo Nordisk. There is no duality of interest associated with this manuscript.

References

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Philippe P. Pagni
    • 1
  • Anitra Wolf
    • 1
  • Mauro Lo Conte
    • 1
  • Ronald Yeh
    • 1
  • Guangsen Fu
    • 1
  • Fa Liu
    • 1
  • Matthias von Herrath
    • 1
  • Ken Coppieters
    • 2
    Email author
  1. 1.Novo Nordisk Research CenterSeattleUSA
  2. 2.Novo Nordisk A/S Research ProjectsMåløvDenmark

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