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Cover Page

The handle

http://hdl.handle.net/1887/68231

holds various files of this Leiden University

dissertation.

Author: Engelberts, P.J.

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Cover art Joost Bakker, scicomvisuals, Amsterdam, The Netherlands Production Joost Bakker, scicomvisuals, Amsterdam, The Netherlands Design & Dtp De vliegende kiep,

Amsterdam, The Netherlands Printed by

Ipskamp Printing, Enschede ISBN/EAN: 978 94 028 1260 2 Proefschrift Universiteit Leiden, Faculteit Geneeskunde

© 2018, Petrus Johannes Engelberts, The Netherlands

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proefschrift

Ter verkrijging van de graad van doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens het besluit van het College voor Promoties te verdedigen op

donderdag 10 Januari 2019 klokke 16:15 uur

door

Petrus Johannes Engelberts

Geboren op 17 September 1975,

te Utrecht

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Promotor

Prof. Dr. P.W.H.I. Parren Co-promotor Dr. E.C.W. Breij Promotiecommissie Prof. Dr. M. de Haas Prof. Dr. J.J.C. Neefjes Dr. T. van Hall

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Table of Contents

Chapter 1 General outline and aim of the thesis 9

Chapter 2 The evolution of immunotherapy: lessons learned from targeting CD20 19

Chapter 3 A quantitative flow cytometric assay for determining binding characteristics of chimeric, humanized and human antibodies in whole blood: proof of principle with rituximab and ofatumumab 77

Chapter 4 Type I CD20 antibodies recruit the B-cell receptor for complement-dependent lysis of malignant B cells 99

Chapter 5 Ibrutinib interferes with the cell-mediated anti-tumour activities of therapeutic CD20 antibodies: implications for combination therapy 125 Chapter 6 DuoBody®-CD3xCD20, an Fc-silenced whole IgG

T cell retargeting bispecific antibody, displays unique capacity to induce T-cell mediated kill of malignant B cells, and provides opportunities for subcutaneous dosing 147

Chapter 7 General discussion of the thesis 187

Summary 217

Samenvatting in het Nederlands 219

Dankwoord 222

Publications 224

Abbreviations 226

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