Background: Selective neutralization of the IL21/IL21R signaling pathway is a promising approach for the treatment of a variety of autoimmune diseases. Ab-01 is a human neutralizing anti-IL21R antibody. In order to ensure that the activities of Ab-01 are restricted to neutralization even under in vitro cross-linking and in vivo conditions, a comprehensive assessment of agonistic potential of Ab-01 was undertaken.Methods: In vitro antibody cross-linking and cell culture protocols reported for studies with a human agonistic antibody, TGN1412, were followed for Ab-01. rhIL21, the agonist ligand of the targeted receptor, and cross-linked anti-CD28 were used as positive controls for signal transduction. In vivo agonistic potential of Ab-01 was assessed by measuring expression levels of cytokine storm-associated and IL21 pathway genes in blood of cynomolgus monkeys before and after IV administration of Ab-01.Results: Using a comprehensive set of assays that detected multiple activation signals in the presence of the positive control agonists, in vitro Ab-01-dependent activation was not detected in either PBMCs or the rhIL21-responsive cell line Daudi. Furthermore, no difference in gene expression levels was detected in blood before and after in vivo Ab-01 dosing of cynomolgus monkeys.Conclusions: Despite efforts to intentionally force an agonistic signal from Ab-01, none could be detected. © 2010 Guo et al; licensee BioMed Central Ltd.
CITATION STYLE
Guo, Y., Hill, A. A., Ramsey, R. C., Immermann, F. W., Corcoran, C., Young, D., … O’Toole, M. (2010). Assessing agonistic potential of a candidate therapeutic anti-IL21R antibody. Journal of Translational Medicine, 8. https://doi.org/10.1186/1479-5876-8-50
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