CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor. Reply to Pagni PP, Wolf A, Lo Conte M et al [letter]
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To the Editor: We appreciate the letter by Pagni et al  that comments on our previous publication . However, rather than definitively demonstrating that the KGYY15 peptide does not work in pre-clinical studies, their report highlights the complexities of CD40 as a molecule and strengthens the need for a better understanding of CD40. It is easy to think that a molecule that has been studied for so long is fully understood when in reality the opposite is true.
The CD40 molecule has, over time, proven to be more complex than a simple cell-identifying molecule. Tone et al  demonstrated the existence of CD40 isoforms that were generated through alternative splicing of its RNA. We subsequently showed that there are differentially glycosylated forms of CD40 and those that are less glycosylated appear to represent a more active form of the protein . In addition, we demonstrated that CD40 can form hybrid receptors with TNF-receptors 1 and 2. Further, we reported that CD40 interacts...
KeywordsAutoimmunity CD154 CD40 Therapeutic Type 1 diabetes
Recombination activating gene
GMV was responsible for drafting the article and DHW revised it critically for important intellectual content. All authors approved the version to be published.
Duality of interest
DHW is the founder and Chief Science Officer of Op-T LLC. DMW is the Chief Financial Officer of Op-T LLC. GMV performs consulting work for Op-T LLC.
- 1.Pagni PP, Wolf A, Lo Conte M et al (2019) CD40-targeted peptide proposed for type 1 diabetes therapy lacks relevant binding affinity to its cognate receptor. Diabetologia. https://doi.org/10.1007/s00125-019-4893-2