Presents timely and authoritative information on the development of precision cancer therapies as applied to hematologic malignancies

The Precision Cancer Therapies series focuses on how to understand and translate fundamental basic science into information that can be directly applied to patients to advance care. Each volume of the series integrates the relevant biological concepts and principles necessary for translating this science to practitioners of this science.

Precision Cancer Therapies, Volume Two, focuses on sophisticated immunotherapies targeting cancers affecting the blood, bone marrow, and lymph nodes. Edited and authored by the foremost authorities in the field, this comprehensive reference text covers targeting of cell surface receptors, antibody-drug conjugates (ADC), targeting immune checkpoint, targeting macrophages, EBV-directed immunotherapies, tumor-associated antigens (TAA), and chimeric antigen receptor T-cells (CAR-T).

Divided into nine sections, Volume Two includes an overview of the history of immunotherapy development in cancer, as well as a concluding section addressing the mechanistic basis and role of immunomodulatory drugs, analytical tools to quantitate immune-mediated effects, and other topics in immunotherapy. Chapters on specific therapeutics or therapeutic classes include a basic explanation of the underlying pathway and target, the pharmacology of the drug/class, relevant preclinical and clinical data, and discussion of clinical management and potential predictive biomarkers of response. This book also:

• Delivers a definitive, state-of-the-art review of the relevant biology and its importance in the broader context of cancer biology
• Focuses on agents that mediate cell killing in lymphoma through a variety of immunologic mechanisms
• Covers FDA-approved drugs and their indications, as well as drugs currently in development
• Provides information on monotherapy and combination therapy, summary tables of trials, and discussion of toxicity and efficacy
• Includes boxed sections highlighting major unique points about the information in the chapter

Precision Cancer Therapies, Volume Two: Immunologic Approaches for the Treatment of Lymphoid Malignancies, From Concept to Practice is an indispensable resource for medical, scientific, and allied medical professionals, advanced students, and interested general readers with background knowledge in the subject.

List of Contributors xix

Volume Foreword xxiv

Volume Preface xxvi

Series Preface xxviii

Section I Historical Perspective 1

1 The Distinguished History of Immunotherapy Development in Cancer 3
Stephen M. Ansell

Section II Targeting Cell Surface Receptors 9

2 Development of Monoclonal Antibodies for the Treatment of Lymphoma: Setting the Stage 11
George J. Weiner

3 Pharmacology to Practice: The Similarities and Differences of Drugs Targeting CD20 22
Jennifer K. Lue and Bruce D. Cheson

4 Pharmacology to Practice: Targeting CD19 and 22 40
Nilanjan Ghosh and Sonali M. Smith

5 Targeting Other Promising Cell Surface Receptors: ROR1, CD38, CD25, and CCR4 52
Michael Wang

Section III Antibody Drug Conjugates (ADC) 73

6 Principles of Antibody Drug Development 75
Eric L. Sievers

7 Targeting CD30 in Lymphoid Neoplasms 87
Barbara Pro

8 Targeting CD79b in B-cell Malignancies 100
Colette Owens and Gilles Salles

9 Radioimmunotherapy: Is There Any Future Role? 108
Alessandro Broccoli and Pier Luigi Zinzani

Section IV Targeting Immune Checkpoint 123

10 The Biology of Immune Checkpoint Blockade 125
Timothy N. Bullock

11 Mechanism of Action and Pharmacologic Features of Drugs Targeting PD-1/PDL-1 and CTLA-4 139
Marc-Anthony Rodriguez, Ryan Bucktrout, Andrea Orlando, Inna Serganova, and Roberta Zappasodi

12 Other Immune Checkpoint Targets of Interest 156
Clifford M. Csizmar and Stephen M. Ansell

13 Clinical Experiences with Immune Checkpoint Inhibitors in Lymphomas 190
John M. Timmerman

Section V Targeting Macrophages and SIRP-α – Disrupting the "Do Not Eat Me" 209

14 The Role of CD47 in Lymphoma Biology and Strategies for Therapeutic Targeting 211
Mithunah Krishnamoorthy, Robert A. Uger, and Mark Wong

15 Single Agent and Rational Combination Experiences with Anti-CD47 Targeted Drugs 225
Nadia Khan, Swathi Namburi, and Krish Patel

Section VI EBV Directed Immunotherapies 233

16 Understanding the Role of EBV Infection in Lymphomagenesis 235
Hiroshi Kimura and Takayuki Murata

17 Immunologic Therapies in Development for EBV Driven Lymphoid Malignancies 246
Jason Yongsheng CHAN, Seok Jin Kim, Soon Thye LIM, Choon Kiat ONG, and Won Seog Kim

Section VII Exploiting Tumor Associated Antigens with Autologous T-Cells 257

18 The Scientific Rationale for Targeting Tumor-Associated Antigens 259
Jean-Sébastien Delisle and Marie-France Aubin

19 Clinical Experiences with TAA-T in Lymphoid Malignancies 276
Keri Toner, Hannah Kinoshita, and Catherine M. Bollard

Section VIII Chimeric Antigen Receptor T-Cells (CAR-T) 289

20 The Science of CAR-T Cell Technology 291
Richard C. Godby, Allison M. Bock, Saad S. Kenderian, and Yi Lin

21 The Spectrum of CAR T Assets in Development: Similarities and Differences 304
J. Erika Haydu and Jeremy S. Abramson

22 Clinical Experience with CAR-T Cells for Treatment of B-cell Lymphomas 318
Stephen J. Schuster and John G. Gribben

23 "Off the Shelf" CAR-T/NK Cells 341
Nancy D. Marin, Alice Zhou, Miriam T. Jacobs, and Todd A. Fehniger

24 Programming Myeloid Cells with Chimeric Antigen Receptor Myeloid-Based Therapies 360
Miriam Barnett, Michele Gerber, Siddartha Mukherjee, and Daniel Getts

Section IX Miscellaneous Topics in Immunotherapy 373

25 Mechanistic Basis and Role of Immunomodulatory Drugs 375
John G. Gribben

26 Analytical Tools to Quantitate Immune Mediated Effects: What Should We Measure and How? 384
Kevin D. Pavelko and Jose C. Villasboas

27 The Role of the Microbiome in Immune Response 397
Máire A. Conrad, Kathleen E. Sullivan, and Judith Kelsen

28 Epigenetic Drugs as Modulators of Tumor Immunogenicity and Host Immune Response 406
Enrica Marchi, Ipsita Pal, John Sanil Manvalan, Kallesh Danappa Jayappa, and Owen A. O`Connor

29 Tailoring Specific Radiographic Response Criteria for Immunologic Therapies in Lymphoma 429
Bruce D. Cheson

Conclusions 433

Must Reads 433

References 433

Index 436

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