"Optimizing an effective antitumor immune response has always been the goal of immunological strategies to treat cancer. It has been known for many years that the immune system plays a central role in cancer development and control; and promoting the immune response may be of profound therapeutic value. Patients with evidence of immunosuppression are at higher risk for cancer and while spontaneous remissions in certain cancers are uncommon, they are a well-recognized phenomenon. Additionally, there are reports of patients whose malignancy regressed at the time of an infectious episode suggesting that activation of the immune system promoted an anti-tumor effect. Furthermore, many indolent lymphomas follow a 'waxing and waning' course suggesting that the immune system may modulate progression of the disease. Understanding the components of an effective antitumor immune response, and developing strategies to optimize them, has led to remarkable advances in the treatment of cancer, particularly lymphoid malignancies. Some of the key steps in this process are highlighted below and the various components of immunotherapy in use to treat patients are discussed in the chapters that follow"--
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- 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
Mįire 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
OWEN A. OCONNOR, MD, PhD, American Cancer Society Research Professor; Professor of Medicine, University of Virginia Cancer Center, Charlottesville, VA, USA.
STEPHEN M. ANSELL, MD, PhD, Consultant, Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
JOHN G. GRIBBEN, MD, DSc, Hamilton-Fairley Chair of Medical Oncology, Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, UK.
