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Enhancing IgG fragment crystallizable sialylation improves the therapeutic activity of IL-23 cytokine blockade
Sebastian Kämpf, Marjan Hematianlarki, Leon Altmann, Jessica M. Bright, Alyssa M.A. Toda, Zohreh Mirzapoor, Valentin Zollner, Anja Werner, Johanna Bulang, Barbara Radovani, Miriam Wöhner, William Avery, Mark J. Karbarz, Pamela B. Conley, Greg P. Coffey, Falk Nimmerjahn
Sebastian Kämpf, Marjan Hematianlarki, Leon Altmann, Jessica M. Bright, Alyssa M.A. Toda, Zohreh Mirzapoor, Valentin Zollner, Anja Werner, Johanna Bulang, Barbara Radovani, Miriam Wöhner, William Avery, Mark J. Karbarz, Pamela B. Conley, Greg P. Coffey, Falk Nimmerjahn
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Research Letter Immunology Inflammation

Enhancing IgG fragment crystallizable sialylation improves the therapeutic activity of IL-23 cytokine blockade

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Abstract

Authors

Sebastian Kämpf, Marjan Hematianlarki, Leon Altmann, Jessica M. Bright, Alyssa M.A. Toda, Zohreh Mirzapoor, Valentin Zollner, Anja Werner, Johanna Bulang, Barbara Radovani, Miriam Wöhner, William Avery, Mark J. Karbarz, Pamela B. Conley, Greg P. Coffey, Falk Nimmerjahn

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Figure 1

Immunomodulatory activity of IL-23–specific antibody variants in rheumatoid arthritis.

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Immunomodulatory activity of IL-23–specific antibody variants in rheumat...
(A) Schematic representation of the IL-23–specific human hypersialylated (α2,6) IgG1 antibody with the F241A mutation (IL-23–IgG1–F241A). (B and C) Clinical scores (mean ± SEM) (B) or area under the curve (AUC) of clinical scores (box-and-whiskers plot) (C) of joint inflammation in KBxN mice treated with PBS or the indicated doses of human IL-23–IgG1, IL-23–IgG1–F241A, or TNP-specific IgG1-F241A antibodies. Depicted is the combination of 2 independent experiments with n = 6–12 mice per group. For statistical analysis, an ordinary 1-way ANOVA and a Dunnett’s multiple-comparison test were used. ***P < 0.001, ****P < 0.0001. (D and E) Quantification of bone erosions (in mm2) (D) and of the number of TRAP+ osteoclasts (E) on the surface of bone erosions in histological samples of KBxN mice treated with PBS or the respective amounts of the IL-23–IgG1, IL-23–IgG1–F241A, or TNP-IgG1-F241A antibody. Shown are all data points and the mean ± SEM of the combination of 2 independent experiments (n = 5–6 mice per group). For statistical analysis, a 2-way ANOVA and a Tukey’s multiple comparisons test were used. ***P < 0.001, ****P < 0.0001. (F) Clinical scores of KBxN mice treated with the indicated amounts of IL-23–IgG1, IgG1-F241A-Fc, IL-23–IgG1 + IgG1-F241A-Fc, IL-23–IgG1–F241A, or PBS. Statistically significant differences against PBS treatment were identified by using a 2-way ANOVA and Šídák’s multiple-comparison test. Depicted is the mean ± SEM of the combination of 2 independent experiments (n = 5–10 mice per group). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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