NK Cells in Cancer Immunotherapy: Successes and Challenges

NK Cells in Cancer Immunotherapy: Successes and Challenges explains the latest immunotherapeutic strategies, focusing on NK cells to allow the best and precise combination treatments to cancer patients. The book provides existing background knowledge in the field of immunotherapy and discusses future areas of research required to carry out cutting-edge, validated therapies. Chapters cover advances in immunotherapeutic strategies, in particular, the use of NK cells with and without T-cell therapy in the treatment of cancer. The book is a valuable resource for cancer researchers, oncologists, graduate students and those interested in learning more about novel strategies to treat cancer patients.

Immunotherapy is fast becoming the method of choice for cancer therapy. Although remarkable advances have been made in the field of immunotherapy, there are significant challenges and difficulties ahead since many of the current immunotherapeutic strategies do not provide long-lasting treatment strategies, and therefore are not very effective.

Cover
Title page
Table of Contents
Copyright
Cover Image Insert
Hypothetical role of NK cells in differentiation of tumor cells, increased susceptibility of tumor cells to chemotherapy or radiation and lower risk of metastasis
Aims and Scope of Series “Breaking Tolerance to Anti-Cancer Cell-Mediated Immunotherapy”
About the Series Editor
Aims and Scope of Volume
About the Volume Editors
Preface—Cellular immunotherapies: Evolution from laboratory studies to effective human therapies
Contributors
Section I: Basics of cellular immunotherapy: Differing roles of NK and T cells in targeting cancer and their intimate synergistic interaction underscores the requirement for the use of both cell types in successful cancer treatment
Chapter 1: Multifaceted nature of natural killer cells: Potential mode of interaction and shaping of stem cells
Abstract
Acknowledgments
Conflict of interest
Natural killer cells: Overview and background
Two faces of NK cells: Concept of split anergy in NK cells and its potential role in tumor differentiation
The rationale for the functional activation of NK cells in many gene knockout mice: Potential common mechanism of activation
Dysfunctional NK cells in cancer patients: Defects in NK cells to lyse and differentiate CSCs
Suppression of antitumor immune function and change in NK cell phenotype in tumor microenvironment: Could compromised NK function lead to dysregulated immune function in tumor microenvironment?
Tumor-associated stromal cells may shape the function of NK cells
Function of NK cells in tumor-bearing humanized-BLT mice mirrors those of the cancer patients
Novel strategy to expand supercharged NK cells for immunotherapy using osteoclasts as feeder cells: Different efficacy of supercharged NK cell expansion and function using allogeneic vs autologous NK cells from healthy or cancer patients
Supercharged NK cells differ from primary NK cells in phenotype and function
Supercharged NK cells preferentially and rapidly expand CD8 + T cells
Functional differences of NK cells in different NK expansion platforms against CSCs/poorly differentiated tumor cells: Comparison with supercharged NK cells
Immunotherapy is essential in combination with chemotherapy: Chemotherapy targets differentiated tumors more than cancer stem-like cells
Combination of NK cell and antibody therapy: NK cells can target CSCs and their differentiated counterparts through direct lysis and/or ADCC, respectively
NK cells and the oncolytic viruses
Combination therapy with NK cells and immune checkpoint inhibitors
Conclusions
References
Chapter 2: Reversing the NK inhibitory tumor microenvironment by targeting suppressive immune effectors
Abstract
Conflict of interest
Introduction
Dysregulation of NK cell immune responses by the tumor microenvironment
Suppressive immune effectors of the tumor microenvironment
Techniques to evaluate the tumor microenvironment
Advancements in therapeutic modalities to overcome TME suppression
Perspectives and conclusions
References
Chapter 3: Natural killer cells as immunotherapeutic effectors for solid tumors
Abstract
Conflict of interest
Introduction
Sources of NK cells for immunotherapy (Table 1)
Challenges to NK cell immunotherapy in solid tumors (Table 2)
Genetic engineering of NK cells
Conclusions
References
Chapter 4: Targeting NKG2D/NKG2D ligand axis for cancer immunotherapy
Abstract
Conflict of interest
Introduction
NKG2D
NKG2D in antitumor immunity
Conclusions
References
Chapter 5: Chimeric antigen receptor-modified cells for the treatment of solid tumors: First steps in a thousand-mile march
Abstract
Acknowledgments
Conflict of interest
Introduction
CAR T-cell therapy experience in solid tumors
Overcoming challenges facing CAR therapy in solid tumors
Beyond CAR T-cell therapy
Conclusion
References
Chapter 6: Tumor-infiltrating lymphocyte (TIL) therapy
Abstract
Acknowledgments
Conflict of interest
Introduction
Improving antitumor efficacy of TIL ACT by targeting neoantigens
Impact of cellular phenotype upon TIL ACT longevity
Improvement in TIL manufacturing and modern-day clinical trials
TILs and solid tumors other than melanoma
Summary
References
Chapter 7: Biology and status of chimeric antigen receptor-engineered T cell therapy
Abstract
Conflict of interest
Introduction
Generations of CAR T cells
FDA approved CAR T cells in hematologic malignancies
Challenges in solid tumor targeting with CAR T cell therapy
Physical and metabolic barriers in the solid tumor microenvironment
The immunosuppressive TME
Solid tumor antigen heterogeneity and antigen escape
Future perspective of CAR T cell therapy approaches to tackle solid tumors
References
Section II: Process and trials optimization: Diagnostics, readouts, route, and production to optimize cell therapy
Chapter 8: Optimization of production for cell therapies
Abstract
Conflict of interest
Keep the end goal in mind from early stage: Define the target product profile
Process design: Take a quality by design approach
Get to the goal: Many decisions to make
Understand the analytical needs
Identify and overcome the distribution, thawing, and dispensing challenges
Conclusion
References
Chapter 9: Lymphodepletion and cellular immunotherapy
Abstract
Conflict of interest
Introduction
Solid tumors
Conclusion
References
Chapter 10: Imaging the immune cell in immunotherapy
Abstract
Acknowledgments
Conflict of interest
Imaging objectives from an immunological perspective
Imaging modalities and labeling strategies for cancer immunotherapy
Application of the “Imaging Toolbox” toward cancer immunotherapy
What the future holds
References
Chapter 11: Radiologic assessment of tumor response to immunotherapy and its complications
Abstract
Acknowledgments
Conflict of interest
Introduction
Uses of medical imaging in immunotherapy
Challenges to medical imaging presented by immunotherapy
Methods of measurement of tumor response
Future directions for imaging tumor response to immunotherapy
Conclusions
References
Chapter 12: Novel cell delivery systems: Intracranial and intrathecal
Abstract
Conflict of interest
Tumors of the central nervous system
Blood brain barrier (BBB)
Direct delivery
Methods to disrupt the BBB
Conclusion
References
Chapter 13: Diagnostic methods to assess the numbers, phenotype, and function of primary and engineered NK cells: Methods to predict prognosis and treatment outcome
Abstract
Conflict of interest
Introduction
Major parameters to assess NK cell functions
Methodologies to assess NK cell surface markers, cytotoxicity, and secretion
Significance of NK cell diagnostics in the field of cancer
NK cell diagnostics: Future of cancer diagnostics
References
Section III: Patient trials and combinational strategies in cellular immunotherapy; Successful cell therapy may depend on the selection of treatment strategies synergistic with cell therapy
Chapter 14: Combination of NK cell immunotherapy with chemotherapy and radiation enhances NK cell therapy and provides improved prognosis in cancer patients and in humanized BLT mouse model system
Abstract
Acknowledgments
Author contributions
Statement of originality
Conflict of interest statement
Introduction
Preclinical and clinical development of NK cell-based immunotherapies
Rationale for NK cell-based immunotherapy
Rationale for combination of chemotherapy with NK-based therapy
Combination of cisplatin with supercharged NK cell immunotherapy enhances NK cell mediated killing and increases the secretion of IFN-γ in humanized-BLT mice
Rationale for combination of targeted therapy with NK-based therapy
Rationale for combination of radiation therapy and NK cell therapy
Conclusion
References
Chapter 15: Combining oncolytic viruses with immune cell therapy as treatments for cancer: OV, CAR T-cell, and NK combinations
Abstract
Conflict of interest
Introduction
CAR-T cell therapy and oncolytic viruses in cancer therapy
NK cells and oncolytic viruses in cancer therapy
Immune cells as carriers of OV in cancer therapy
Conclusion
References
Chapter 16: Natural killer cells in the treatment of glioblastoma: Diverse antitumor functions and potential clinical applications
Abstract
Acknowledgments
Author contributions
Conflict of interest
Introduction
Natural killer cells: Basic biology and dysfunction in cancer
Use of natural killer cell-based therapeutic platforms for cancer immunotherapy
Glioblastoma remains an incurable primary brain tumor
Natural killer cell-based immunotherapy for primary brain tumors
Preclinical tumor models and the translation of natural killer cell therapy into the clinic
Conclusions and future directions
References
Chapter 17: Immunotherapy using CAR T: What we have learned from trials and where we are heading
Abstract
Conflicts of interest
Funding support
Disclosures
Landscape of CAR T-cell clinical trials
New developments in CAR design
CAR T-cell trials vs ICI trials
Lessons learned in optimizing the clinical flow of CAR T-cell trials
Development of institutional infrastructure to conduct successful CAR T-cell trials
I. Standardized workflows across the institution that are flexible to different disease models and CAR constructs
II. Standardized grading and treatment algorithms for the management of CRS and neurotoxicity
III. Interdisciplinary collaboration
IV. Research and ancillary support
V. Ongoing education
Where we are heading
References
Chapter 18: NKT cell: Success and promises in transplantation and immunotherapy
Abstract
Acknowledgments
Conflict of interest
Biology of NKT cells
Mechanisms and relevant studies of iNKT cells suppressing GvHD in allogeneic transplantation
Mechanisms of iNKT cells in antitumor immunity
Regulation of antitumor effector cells
iNKT cell-based immunotherapy for treating cancer
Challenges and perspectives
References
Chapter 19: Tumor-infiltrating lymphocytes: Prognostic considerations and current trials as adoptive cell therapy
Abstract
Conflict of interest
Introduction
History of ACT
TILs as a prognostic factor for survival in selected cancers
Preparation of TIL for ACT
ACT therapy
Safety and tolerability of ACT
Future directions
References
Chapter 20: Molecular remission using personalized low-dose immunotherapy with minimal toxicities for poor prognosis hematological and solid tumor cancers
Abstract
Conflict of interest
Introduction
Case reports
Discussion
Conclusions
Future perspectives
References
Index

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Physical Sciences & Engineering

Social Sciences & Humanities

Health

NK Cells in Cancer Immunotherapy: Successes and Challenges

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