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Merck

Generation and characterization of human anti-human IL-21 neutralizing monoclonal antibodies.

mAbs (2012-02-14)
Mark F Maurer, Ursula Garrigues, Stephen R Jaspers, Brent Meengs, Mark W Rixon, Brenda L Stevens, Kenneth B Lewis, Susan H Julien, Thomas R Bukowski, Anitra C Wolf, Nels B Hamacher, Mark Snavely, Stacey R Dillon
RESUMEN

Interleukin-21 (IL-21) is a type I four-helical bundle cytokine that exerts a variety of significant effects on many hematopoietic cells, including T and B lymphocytes and natural killer cells. IL-21 is produced predominantly by CD4+ T cells and natural killer T cells and, when aberrantly overexpressed, appears to play important roles in a wide variety of autoimmune disorders. To generate potential therapeutic reagents capable of inhibiting IL-21 for clinical use, we immunized human immunoglobulin transgenic mice with IL-21 and then identified and cloned a panel of human anti-human IL-21 binding monoclonal antibodies. IL-21 neutralizing and IL-21-binding, non-neutralizing antibodies were assigned to distinct epitope "bins" based on surface plasmon resonance competition studies. The most potent neutralizing antibodies had extremely high (sub pM) affinity for IL-21 and were able to block IL-21 activity in various biological assays using either an IL-21R-transfected pre-B-cell line or primary human B cells, and their neutralizing activity was, in some cases, superior to that of a soluble form of the high affinity heterodimeric IL-21 receptor. Characterization of this panel of IL-21 antibodies provided the basis for the selection of a therapeutic candidate antibody capable of inhibiting IL-21 activity for the treatment of autoimmune and inflammatory diseases.

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Roche
BM Condimed H1, Hybridoma Cloning Supplement
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