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Immunogenicity of therapeutic antibodies
Immunological mechanisms & clinical consequences
van Schie, K.A.J.
Publication date
2017
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Citation for published version (APA):
van Schie, K. A. J. (2017). Immunogenicity of therapeutic antibodies: Immunological
mechanisms & clinical consequences.
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Immunogenicity of therapeutic antibodies
Immunological mechanisms & clinical consequences
Life Sciences, Sanquin Research, and the Dutch Arthritis Foundation. Copyright © Karin van Schie, 2017
ISBN: 978-94-6233-737-4 Cover design: Bruce de Kok
Immunogenicity of therapeutic antibodies
Immunological mechanisms & clinical consequences
ACADEMISCH PROEFSCHRIFTter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus
prof. dr. ir. K.I.J. Maex
ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel
op donderdag 12 oktober 2017, te 14.00 uur
door
Katharina Anna Jacoba van Schie
Copromotores: Dr. T. Rispens Sanquin Research
Dr. G.J. Wolbink Reade
Overige leden: Prof. dr. J. Borst Universiteit van Amsterdam Prof. dr. R.E.M. Toes Universiteit Leiden
Prof. dr. W. Jiskoot Universiteit Leiden
Prof. dr. G.R.A.M. D’Haens Universiteit van Amsterdam Prof. dr. A. Gils Katholieke Universiteit Leuven Prof. dr. R.F. van Vollenhoven Universiteit van Amsterdam
TABLE OF CONTENTS
Chapter 1 General introduction 7
Chapter 2 Cross-reactive and pre-existing antibodies to therapeutic antibodies—Effects on treatment and immunogenicity
29
Chapter 3 Therapeutic TNF inhibitors can differentially stabilize trimeric TNF by inhibiting monomer exchange
55
Chapter 4 The antibody response against human and chimeric anti-TNF therapeutic antibodies primarily targets the TNF binding region
79
Chapter 5 Neutralizing capacity of monoclonal and polyclonal anti-natalizumab antibodies: The immune response to antibody therapeutics preferentially targets the antigen-binding site
95
Chapter 6 Infusion reactions during infliximab treatment are not associated with IgE anti-infliximab antibodies
113
Chapter 7 Complexes of drug and anti-drug antibodies cause limited immune activation due to a restricted anti-idiotype response
135
Chapter 8 Summarizing discussion 171
Appendix English summary 197
Nederlandse samenvatting 200
List of publications 203
List of co-authors and their contribution to the manuscript 205
Portfolio 209
Curriculum Vitae 211
