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

Excerpt

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]. …