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Different adaptations of IgG effector function in human and non-human primates and implications for therapeutic antibody treatment

Warncke, Max and Calzascia, Thomas and Coulot, Michele and Balke, Nicole and Touil, Ratiba and Kolbinger, Frank and Heusser, Christoph (2012) Different adaptations of IgG effector function in human and non-human primates and implications for therapeutic antibody treatment. Journal of Immunology. ISSN 0022-1767

Abstract

Safety of human therapeutic antibodies is generally assessed in non-human primates. While IgG1
shows identical FcγR interaction and effector function profile in both species, fundamental
differences in the IgG2 and IgG4 antibody subclasses were found between the two species.
Granulocytes, the main effector cells against IgG2 and IgG4 opsonized bacteria and parasites, do
not express FcγRIIIb, but show higher levels of FcγRII in cynomolgus monkey. In humans, IgG2
and IgG4 adapted a silent Fc region with weak binding to FcγR and effector functions, whereas in
contrast cynomolgus monkey IgG2 and IgG4 display strong effector function as well as
differences in IgG4 Fab arm exchange. To balance this shift toward activation, the cynomolgus
inhibitory FcγRIIb shows strongly increased affinity for IgG2. In view of these findings, in vitro
and in vivo results for human IgG2 and IgG4 obtained in the cynomolgus monkey have to be
cautiously interpreted, whereas effector function related effects of human IgG1 antibodies are
expected to be predictable for man.

Item Type: Article
Related URLs:
Additional Information: Depending on the publisher, we will have to deposit the in-house generated cynomolgus IgG sequences in a public database. Amgen already published similar sequences in a Patent
Keywords: Fc receptor IgG Antibody Effector Function IgG4 Fab Arm exchange cynomolgus non-human primate immunity
Related URLs:
Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6734

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