Antibody-Drug Conjugates and Immunotoxins: From Pre-Clinical Development to Therapeutic Applications

370 Pages·2013·6.17 MB·English

by  Pamela A. Trail (auth.)

Cancer Drug Discovery and Development
Series Editor
Beverly A. Teicher
National Cancer Institute, Rockville, MD, USA
For further volumes:
http://www.springer.com/series/7625

Gail Lewis Phillips
Editor
Antibody-Drug Conjugates
and Immunotoxins
From Pre-Clinical Development
to Therapeutic Applications
Editor
Gail Lewis Phillips
Genentech, Inc.,
South San Francisco, CA, USA
ISBN 978-1-4614-5455-7 ISBN 978-1-4614-5456-4 (eBook)
DOI 10.1007/978-1-4614-5456-4
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2012948341
© Springer Science+Business Media New York 2013
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This book is dedicated to the memory of
Dr. Ralph Schwall and to my mentor,
colleague, and friend, Dr. Mark Sliwkowski,
for their unwavering belief in the promise
of antibody–drug conjugates for targeted
cancer therapy.
Gail Lewis Phillips, Editor

Contents
Part I Introduction and Development Perspectives
1 Antibody Directed Delivery for Treatment of Cancer:
Antibody Drug Conjugates and Immunotoxins ................................. 3
Pamela A. Trail
2 Antibody–Drug Conjugate Development ............................................ 23
Aakanksha Khandelwal, Haleh Saber, Marjorie A. Shapiro,
and Hong Zhao
Part II Development of Antibody-Drug Conjugates
3 Assay Methodologies and Challenges .................................................. 41
Katherine R. Kozak and Helga Raab
4 Clinical Pharmacology Strategies in the Development
of Antibody–Drug Conjugates ............................................................. 57
Sandhya Girish and Manish Gupta
5 Predictive Biomarkers for Antibody–Drug Conjugates .................... 77
David Dornan and Jeff Settleman
Part III Selection of Cytotoxic Agents
6 Factors Involved in the Design of Cytotoxic Payloads
for Antibody–Drug Conjugates............................................................ 93
Wayne C. Widdison and Ravi V.J. Chari
vii
viii Contents
7 Linker Technology and Impact of Linker Design
on ADC Properties ................................................................................ 117
Victor S. Goldmacher, Rajeeva Singh, Thomas Chittenden,
and Yelena Kovtun
Part IV Antibody-Drug Conjugates for Hematologic Malignancies
8 Antibody–Drug Conjugates for the Treatment
of B-Cell Malignancies .......................................................................... 139
Andrew G. Polson
9 Targeting CD19 with SAR3419, an anti-CD19-Maytansinoid
Conjugate for the Treatment of B Cell Malignancies ........................ 149
John M. Lambert, Veronique Blanc, Nathalie Le Bail,
and Anne Bousseau
10 Brentuximab Vedotin (SGN-35) for CD30-Positive
Malignancies .......................................................................................... 161
Andres Forero, Christos Vaklavas, and Albert F. LoBuglio
Part V Antibody-Drug Conjugates for Solid Tumors
11 Trastuzumab Emtansine (T-DM1) for the Treatment
of HER2-Positive Cancer with a Focus on Breast Cancer ................ 179
Hope S. Rugo, Ian E. Krop, and Yu-Waye Chu
12 CDX-011 (Glembatumumab Vedotin, CR011-vcMMAE) ................. 211
Christos Vaklavas, Albert F. LoBuglio, Mansoor Saleh,
Michael Yelin, and Andres Forero
13 Case Study: An Antibody–Drug Conjugate
Targeting MUC16 for Ovarian Cancer ............................................... 221
Douglas Leipold and William G. Mallet
14 EphA2 Immunoconjugate .................................................................... 241
Zhan Xiao, Dowdy Jackson, and David A. Tice
15 Anti-PSMA Antibody–Drug Conjugates and Immunotoxins ........... 255
Philipp Wolf
16 Targeting CD56 (NCAM)-Expressing Neoplasms
with Lorvotuzumab Mertansine .......................................................... 273
John M. Lambert, James O’Leary, Kathleen R. Whiteman,
and Victor S. Goldmacher
Contents ix
Part VI Metabolism
17 Studies on the Metabolism of Antibody–Drug Conjugates ............... 297
Xiuxia Sun and Hans Erickson
Part VII Immunotoxins
18 Design, Development, and Characterization
of Recombinant Immunotoxins Targeting HER2/neu ....................... 319
Yu Cao and Michael G. Rosenblum
19 The Preclinical and Clinical Evaluation of VB6-845:
An Immunotoxin with a De-Immunized Payload
for the Systemic Treatment of Solid Tumors ...................................... 349
Joycelyn Entwistle, Mark Kowalski, Jennifer Brown,
Jeannick Cizeau, and Glen C. MacDonald
Index ............................................................................................................... 369