NK Cells in Cancer Immunotherapy: Successes and Challenges

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NK Cells in Cancer Immunotherapy: Successes and Challenges
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Hypothetical role of NK cells in differentiation of tumor cells, increased susceptibility of tumor cells to chemotherapy or ...
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
Contents
Contributors
Section I: Basics of cellular immunotherapy: Differing roles of NK and T cells in targeting cancer and their intimate syn ...
Chapter 1: Multifaceted nature of natural killer cells: Potential mode of interaction and shaping of stem cells
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 fu ...
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 s ...
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: Comp ...
Immunotherapy is essential in combination with chemotherapy: Chemotherapy targets differentiated tumors more than cancer st ...
Combination of NK cell and antibody therapy: NK cells can target CSCs and their differentiated counterparts through direct ...
NK cells and the oncolytic viruses
Combination therapy with NK cells and immune checkpoint inhibitors
Conclusions
Acknowledgments
References
Chapter 2: Reversing the NK inhibitory tumor microenvironment by targeting suppressive immune effectors
Introduction
Dysregulation of NK cell immune responses by the tumor microenvironment
Suppressive immune effectors of the tumor microenvironment
Myeloid-derived suppressor cells
Tumor-associated macrophages
Regulatory T cells
Dendritic cells
Techniques to evaluate the tumor microenvironment
Improvements in tissue analysis and imaging
Cytometric analysis of TME composition and function
Estimating TME composition using gene expression data
Assessing metabolic fitness in the TME
Advancements in therapeutic modalities to overcome TME suppression
Direct targeting of inhibitory immune cells of the TME
Reversing NK cell inhibition by the TME through genetic and nongenetic methods
Perspectives and conclusions
References
Chapter 3: Natural killer cells as immunotherapeutic effectors for solid tumors
Introduction
Sources of NK cells for immunotherapy (Table 1)
Expanding NK cells
Challenges to NK cell immunotherapy in solid tumors (Table 2)
CD73-adenosine
CD155-TIGIT
NKG2A
Genetic engineering of NK cells
Antigen escape and multitargeting CARs
NK cell engagers
Conclusions
References
Chapter 4: Targeting NKG2D/NKG2D ligand axis for cancer immunotherapy
Introduction
NKG2D
Molecular characteristics and signaling
NKG2D ligands
Human NKG2D ligands
Mouse NKG2D ligands
Regulation of NKG2D ligands expression
Transcriptional regulation
Posttranslational regulation
NKG2D in antitumor immunity
NKG2D ligands stimulate tumor immunity
Human tumors shed NKG2D ligands to evade immune response
Strategies to harness NKG2D/NKG2DL for cancer immunotherapy
Targeting MIC shedding to sustain NKG2D immunity
Conclusions
References
Chapter 5: Chimeric antigen receptor-modified cells for the treatment of solid tumors: First steps in a thousand-m
Introduction
CAR T-cell therapy experience in solid tumors
Glioblastoma
Neuroblastoma
Lung cancer
Mesothelioma
Breast cancer
Ovarian cancer
Prostate cancer
Renal cell carcinoma
Sarcoma
Overcoming challenges facing CAR therapy in solid tumors
Tumor microenvironment
Nutrient deprivation
Immunosuppressive substances
Acidity
Hypoxia
Cell-mediated immunosuppression
Prospects
Extracellular matrix barrier
Prospects
CAR-T cell trafficking
Prospects
CAR T-cell persistence
Prospects
Target antigens
Prospects
Beyond CAR T-cell therapy
Conclusion
Acknowledgments
References
Chapter 6: Tumor-infiltrating lymphocyte (TIL) therapy
Introduction
Cytotoxic T lymphocytes mediate antigen-specific antitumor immunity
Tumor immune evasion and T cell exhaustion
Antigen nonspecific T cell immunotherapy approaches
Adoptive cell therapy with autologous TILs (TIL ACT)
Alteration of the immune tumor microenvironment to improves the engraftment of autologous TILs
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
Acknowledgments
References
Chapter 7: Biology and status of chimeric antigen receptor-engineered T cell therapy
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
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
Upstream processing
Downstream processing
Filling and cryopreservation
Understand the analytical needs
Identify and overcome the distribution, thawing, and dispensing challenges
Conclusion
References
Chapter 9: Lymphodepletion and cellular immunotherapy
Introduction
Regimens for lymphodepletion
Tumor-infiltrating lymphocytes (TILs)
Chimeric antigen receptor T-cells (CAR-T cells)
Solid tumors
Toxicity of lymphodepletion
Alternatives to lymphodepletion
Conclusion
References
Chapter 10: Imaging the immune cell in immunotherapy
Imaging objectives from an immunological perspective
Imaging modalities and labeling strategies for cancer immunotherapy
Optical imaging (OI)
Fluorescence imaging (FLI)
Bioluminescence imaging (BLI)
Considerations for optical imaging
Ultrasound imaging (US)
Encapsulated gas microbubbles
Nonmicrobubble contrast agents
Considerations for ultrasound imaging
Magnetic resonance imaging (MRI)
Negative contrast agents
Nuclear-based imaging
Basic principles of direct labeling
Considerations for direct labeling
Basic principles of indirect labeling with reporter genes
Considerations for indirect labeling
Application of the ``Imaging Toolbox´´ toward cancer immunotherapy
Imaging T cell trafficking and persistence
Imaging cytolytic T cells (CTLs)
Imaging chimeric antigen receptor T (CAR-T) cells
Imaging T cell activation
Direct imaging T cell activation biomarkers
Direct imaging of targets related to T cell activation and effector function
Indirect imaging NFAT-mediated T cell activation
Imaging metabolic targets
Imaging the tumor microenvironment (TME)
Imaging of programmed cell death protein 1 (PD-1/CD279)
Imaging of programmed cell death protein ligand 1 (PD-L1/CD274)
Imaging of cytotoxic T lymphocyte-associated protein 4 (CTLA-4/CD152)
Imaging of lymphocyte activation gene 3 protein (LAG3)
Imaging of T cell immunoglobulin and mucin domain-containing protein 3 (TIM3)
Imaging of T cell immunoreceptor with Ig and ITIM domains (TIGIT)
Imaging regulatory T cells (Tregs)
Imaging NK cells
Imaging dendritic cell vaccines
What the future holds
Acknowledgments
References
Chapter 11: Radiologic assessment of tumor response to immunotherapy and its complications
Introduction
Uses of medical imaging in immunotherapy
Challenges to medical imaging presented by immunotherapy
Unconventional patterns of response in immunotherapy
Pseudo progression
Hyperprogression
Dissociated response
Immune-related adverse events
Immune checkpoint inhibitors
CAR T cell therapies
Methods of measurement of tumor response
Conventional tumor response criteria
Immune tumor response criteria
FDG-PET for assessment of CAR T-cell therapy
Future directions for imaging tumor response to immunotherapy
Radiomics and artificial intelligence
Targeted radiopharmaceuticals
Conclusions
Acknowledgments
References
Chapter 12: Novel cell delivery systems: Intracranial and intrathecal
Tumors of the central nervous system
Blood brain barrier (BBB)
Direct delivery
Intranasal delivery
Intracranial delivery to CSF
Lumbar intrathecal delivery
Convection-enhanced delivery
Methods to disrupt the BBB
Chemical disruption of BBB
Mechanical BBB disruption
Conclusion
References
Chapter 13: Diagnostic methods to assess the numbers, phenotype, and function of primary and engineered NK cells:
Introduction
Natural killer cells: Basic biology and background
Dysfunctional NK cells at the preneoplastic stage of tumorigenesis and in cancer patients; defects in multiple NK functions.
Rationale for establishing comprehensive diagnostic and prognostic tests to monitor patient NK cells before and after treatment
Major parameters to assess NK cell functions
Surface biomarkers of NK cells
Cytotoxic function of NK cells
Cytokine, chemokine, and growth factors secreted by NK cells
Transcriptional diversity in NK cells
Activation and expansion of NK cells
Induction of differentiation of tumors by NK cells
Methodologies to assess NK cell surface markers, cytotoxicity, and secretion
Analysis of surface markers on NK cells
Evaluation of NK cell cytotoxicity
Evaluation of cytokine and chemokine release by the NK cells
Evaluation of transcriptional diversity in NK cells
Evaluation of NK cells activation and expansion
Evaluation of NK cells mediated differentiation of tumors
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 ...
Chapter 14: Combination of NK cell immunotherapy with chemotherapy and radiation enhances NK cell therapy and provides impr
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 secret ...
Rationale for combination of targeted therapy with NK-based therapy
Rationale for combination of radiation therapy and NK cell therapy
Conclusion
Acknowledgments
References
Chapter 15: Combining oncolytic viruses with immune cell therapy as treatments for cancer: OV, CAR T-cell, and NK combina ...
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
Introduction
Natural killer cells: Basic biology and dysfunction in cancer
Biology of natural killer cells
Natural killer cell dysfunction in cancer
Use of natural killer cell-based therapeutic platforms for cancer immunotherapy
Glioblastoma remains an incurable primary brain tumor
Therapeutic resistance
Complex immunosuppressive microenvironment
Natural killer cell-based immunotherapy for primary brain tumors
Targeting glioblastoma stem cells
CAR NK cells
Supercharged natural killer cells
Preclinical tumor models and the translation of natural killer cell therapy into the clinic
Three-dimensional glioblastoma stem cell models
Organoids
Animal models
Selection of the source and expansion of natural killer cells for clinical application
Conclusions and future directions
Acknowledgments
References
Chapter 17: Immunotherapy using CAR T: What we have learned from trials and where we are heading
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
Funding support
References
Chapter 18: NKT cell: Success and promises in transplantation and immunotherapy
Biology of NKT cells
Subtypes of NKT cells
Activation of iNKT cells
Effector functions of iNKT cells
Mechanisms and relevant studies of iNKT cells suppressing GvHD in allogeneic transplantation
Murine studies
Human studies
Mechanisms of iNKT cells in antitumor immunity
Direct cytotoxicity against tumor cells
Regulation of antitumor effector cells
Modulation of immunosuppressive TME
iNKT cell-based immunotherapy for treating cancer
α-GalCer-loaded DCs therapy
Autologous adoptive transfer therapy
CAR-iNKT therapy
Stem cell-derived iNKT therapy
Challenges and perspectives
Acknowledgments
References
Chapter 19: Tumor-infiltrating lymphocytes: Prognostic considerations and current trials as adoptive cell therapy
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 hema ...
Introduction
Case reports
Poor prognosis unmutated heavy chain chronic lymphocytic leukemia (U-CLL)
Precursor B-cell acute lymphoblastic leukemia
Basal cell carcinoma
High-grade clear cell carcinoma of the endometrium
Ovarian cancer
Extragonadal germ cell tumor
Breast cancer
Case 1
Case 2
Case 3
Hepatocellular carcinoma
Discussion
Conclusions
Future perspectives
References
Index
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