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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