How does the recombinant human interferon beta induce antibodies in immune tolerant mice?

159 Pages·2013·6.11 MB·English

How does the recombinant human interferon
beta induce antibodies in immune tolerant
mice?
Grzegorz Kijanka
Printing of this thesis was financially suported by:
UIPS, Utrecht Institut of Pharmaceutical Sciences.
How does the recombinant human interferon beta induce antibodies in immune tolerant
mice?
PhD thesis with a summary in Dutch
Department of Pharmaceutics, Utrecht University, The Netherlands
ISBN: 978-90-393-6045-3
Chapter 2: Copyright ©2013. From Pharmaceutical Formulation Development of Peptides
and Proteins by Lars Hovgaard, Sven Frokjaer, Marco van de Weert. Reproduced by
permission of Taylor and Francis Group, LLC, a division of Informa plc.
Chapter 1, 3-8: Copyright © 2013 GM Kijanka.
Design of the cover and illustrations for chapters’ title pages:
Magdalena Kijanka
Printed by CPI Wöhrmann Print Service
How does the recombinant human interferon beta
induce antibodies in immune tolerant mice?
Hoe induceert recombinant humaan interferon beta een
antilichaamrespons in immuuntolerante muizen?
(met een samenvatting in het Nederlands)
Proefschrift
ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag
van de rector magnificus, prof.dr. G.J. van der Zwaan, ingevolge het besluit
van het college voor promoties in het openbaar te verdedigen op maandag 16
december 2013 des middags te 2.30 uur
door
Grzegorz Maciej Kijanka
geboren op 27 februari 1984, te Chrzanow, Polen
Promotor: Prof. dr. H. Schellekens
Co-promotor: Dr. V. Brinks
Studies described in this thesis have been partially funded by F. Hoffmann-La Roche Ltd.,
Basel.

Table of contents.
CHAPTER 1 General introduction. 9
CHAPTER 2 Immunogenicity of therapeutic proteins. 17
CHAPTER 3 Immunogenicity of recombinant human interferon 45
beta in immune tolerant mice is characterized by early
involvement of CD4+ T cells, formation of germinal
centers, but no apparent immunological memory.
CHAPTER 4 The impact of adjuvants and immune suppressants on the 61
production of anti rh interferon beta antibodies in immune
tolerant mice.
CHAPTER 5 Recombinant human interferon beta forms complexes with 79
bacteria - potential risk factor for immunogenicity?
CHAPTER 6 Effect of treatment regimen on the immunogenicity of 97
human interferon beta in immune tolerant mice.
CHAPTER 7 Influence of aggregation and route of injection on the 111
biodistribution of mouse serum albumin.
CHAPTER 8 Summary. 129
APPENDICES Nederlandse samenvatting. 139
Affiliations of corresponding authors. 149
Curriculum Vitae. 151
List of publications. 153
Acknowledgements. 157

CHAPTER 1.

General introduction.
Chapter 1.
10