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Exploiting HLA-alloreactivity in TCR Gene Therapy of B Cell Malignancies

Lorenz Jahn

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Exploiting HLA-alloreactivity in TCR Gene Therapy of B Cell Malignancies

© 2017 Lorenz Jahn, New York

Cover Image: Copyright © 2009 Martin Handford

From WHERE’S WALLY? THE INCREDIBLE PAPER CHASE by Martin Handford

Reproduced by kind permission of Walker Books Ltd, London SE11 5HJ

Printing: Ipskamp Drukkers, Enschede, The Netherlands ISBN: 978-94-028-0555-0

The research described in this thesis was supported by the financial assistance of the Dutch Cancer Society (2010–4832) and the Landsteiner Foundation for Blood Transfusion Research (LSBR0713).

Printing of this thesis was financially supported by Fonds Stimulans and the Jim Reekers Foundation.

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Exploiting HLA-alloreactivity in TCR Gene Therapy of B Cell Malignancies

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 besluit van het College voor Promoties te verdedigen op woensdag 19 april 2017

klokke 15.00 uur door

Lorenz Jahn

geboren te Greifswald, DDR

in 1985

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Promotor:

Prof. dr. J.H.F. Falkenburg

Co-promotor:

Dr. M.H.M. Heemskerk

Leden promotiecommissie:

Prof. dr. T.N.M. Schumacher

Prof. dr. M.J. Kersten

(Universiteit van Amsterdam)

Dr. T. Mutis

(Vrije Universiteit Amsterdam)

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Chapter 1 General Introduction and Aim of the Study

Chapter 2 Generation of CD20-specific TCRs for TCR Gene Therapy of CD20low B-cell Malignancies Insusceptible to CD20-targeting Antibodies

Chapter 3 A CD22-reactive TCR from the T-cell Allorepertoire for the Treatment of Acute Lymphoblastic Leukemia by TCR Gene Transfer

Chapter 4 Therapeutic Targeting of the BCR Associated Protein CD79b in a TCR-based Approach Is Hampered by Aberrant Expression of CD79b

Chapter 5 TCR-based Therapy for Multiple Myeloma and Other B-cell Malignancies Targeting Intracellular Transcription Factor BOB1

Chapter 6 Summary and General Discussion Appendices Nederlandse Samenvatting

Dankwoord Curriculum Vitae List of Publications

7 35

71

95

119

147 169 177 178 179

Contents

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