Natural killer (NK) cells are innate lymphoid cells that have a significant role in regulating the defenses against cancer development and certain viral infections. They are equipped with an array of activating and inhibitory receptors that stimulate or diminish NK cell activity, respectively. Inhibitory receptors include, among others, the MHC class I ligands killer cell immunoglobulin-like receptors (KIR) in humans, and members of the Ly49 family of receptors in mice, and CD94/NKG2A. Activating receptors include cytokine and chemokine receptors, and those that interact with ligands expressed on target cells, such as the natural cytotoxicity receptors or NCRs (NKp30, NKp44 and NKp46), NKG2D, CD244 and DNAM-1. In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL. The killing or sparing of target cells depends on the integration of distinct signals that originate from NK cell receptors. NK cells spare healthy cells that express normal levels of MHC class I molecules and low amounts of stress-induced self-molecules, whereas they kill target cells that down-regulate MHC class I molecules and/or up-regulate stress-induced self-molecules. The latter are common signatures of virus-infected cells and tumors. All the accumulated knowledge on NK cell biology, along with many clinical observations, is driving multiple efforts to improve the arsenal of NK cell-based therapeutic tools in the fight against malignant diseases. Indeed, NK cell-based immunotherapy is becoming a promising approach for the treatment of many cancers. It is well known that NK cells have a significant role in the anti-tumor effect of therapeutic antibodies that use ADCC as a mechanism of action. In addition to this, administration of autologous and allogeneic NK cells after activation and expansion ex vivo is used in the treatment of cancer. Moreover, adoptive transfer of NK cell lines has been tested in humans, and genetically modified NK cells expressing chimeric antigen receptors are being studied in preclinical models for potential use in the clinic.
This is another attempt of InTechOpen to continue the dissemination of international knowledge and experience in the field of immunology. The present book includes a number of modern concepts of specialists and experts in the field of immunotherapy, covering the major topics and analyzing the history, current stage, and future ideas of application of modern immunomodulation. It is always a benefit, but also a compliment, to gather a team of internationally distinguished authors and to motivate them to reveal their expertise for the benefit of medical science and health practice. On behalf of all readers, immunologists, immunogeneticists, biologists, oncologists, microbiologists, virologists, hematologists, chemotherapists, health-care experts, as well as students and medical specialists, also on my personal behalf, I would like to extend my gratitude and highest appreciation to InTechOpen for giving me the unique chance to be the editor of this exclusive book.
|Author||: Anahid Jewett|
|Publisher||: Academic Press|
|Release Date||: 2021-03-15|
|ISBN 10||: 9780128226209|
|Pages||: 350 pages|
NK cells in cancer immunotherapy: Successes and Challenges explains the latest immunotherapeutic strategies focusing on NK cells to allow the best and precise combination treatment to be offered to cancer patients. It provides existing background knowledge in the field of immunotherapy and discusses the future areas of research required to carry out cutting edge validated therapies for 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. This book provides recent advances in the immunotherapeutic strategies, in particular the use of NK cells with and without T cell therapy in the treatment of cancer and discusses the problems and challenges that are facing the field and the practitioners. The book is a valuable resource for cancer researchers, oncologists, graduate students and several members of biomedical field who are interested in learning more about novel strategies to treat cancer patients. Covers CAR/T and CAR/NK and adoptive NK cell therapy with and without T cell therapies Discusses basic biology of NK cells and mouse models of human cancers, and the role of NK cells in metastatic cancer and in cancer stem cells Encompasses information on combination therapies using check point inhibition, adoptive transfer of cytotoxic effector cells, chemotherapeutic drugs and activating and inhibitory antibodies
Successes and Challenges of NK Immunotherapy: Increasing Anti-tumor Efficacy describes the unique therapeutic applications of NK cells to fight cancers and eliminate the bulk and subset of cancer stem cells responsible for metastasis, relapse and recurrences. The book provides information on the development, engineering, mechanisms of action, response to various preclinical models, and applications in various clinical trials. Sections cover the development of highly engineered cytotoxic NK cells, their mechanisms of action, preclinical and clinical applications, the development and application of CAR-NK cells, and new NK-drug conjugates, also emphasizing that activated NK cells can target and kill highly resistant cancer stem cells. Written by the leading experts on NK immunotherapy worldwide, this is a valuable resource for researchers, clinicians and members of the biomedical field who are interested in understanding novel and efficient therapies to fight cancers. Discusses the unique developmental applications of NK immunotherapy against cancers, which differs greatly from other types of immunotherapies Provides up-to-date and highly relevant information through chapters written by the leading researchers in the field Presents a significant number of schematic diagrams for easy understanding and reproducibility
|Author||: Mourad Aribi|
|Publisher||: BoD – Books on Demand|
|Release Date||: 2017-03-22|
|ISBN 10||: 9535130218|
|Pages||: 182 pages|
The book Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders is a synthesis work that discusses two main aspects of autoimmunity: Immunopathogenesis and therapeutic approaches essentially based on the immunotherapies. This book deals with different topics on a number of autoimmune disorders, including type 1 diabetes, autoimmune cardiomyopathy, autoimmunity of gastrointestinal tract, systemic sclerosis, and myasthenia gravis. This book will be useful to clinicians, biologists, researchers, teachers, and students who are interested in immunology and immunopathology.
Immune Surveillance deals with the issues regarding tumor immunology and surveillance, in which the central theme is all about the life span of the mammalian host that is depleted by the environment with mutagenic agents and solutions. The book is divided into six chapters. It includes discussions on the organization and modulation of cell membrane receptors, as well as the origin and expression of membrane antigens. It also covers the topics on the triggering mechanisms for and effector mechanisms activated by the cellular recognition. These topics analyze and evaluate alternatives for the recognition and destruction mechanisms in the knowledge of cell cooperation and requirements for immune recognition. A chapter provides discourse on a solution for the paradox of thriving tumors based on the demonstrable in vitro host immunity. Another discusses the generation of antibody diversity and the theory of self-tolerance. The last chapter explains the evaluation of the evidence for immune surveillance. This reference will be invaluable to those who specialize in immunology.
This volume contains collection of Natural Killer Cell methodologies relevant for both basic and translational research. These methodologies present new developments in the natural killer (NK) cell field, such as understanding the influence of NK cells metabolism on its function, identifying complexity of NK cell subsets through mass cytometry, and determining the emergence of memory NK cells in murine model of MCMV infection. Methods that study NK cell migration and cytotoxicity through endpoint analysis or live single cell imaging are also discussed. Chapters also describe methods pertaining to translational application of NK cells, such as ex vivo expansion of NK cells on K562 cell lines genetically modified to express either membrane bound IL-15 or membrane bound IL-21, large scale NK cell culture, current techniques for engineering NK cells to express chimeric antigen receptors or chemokine receptors using retroviral vectors, electroporation of mRNA, and the natural phenomenon of trogocytosis. Written in the highly successful Methods in Molecular Biology series format, these chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting edge and thorough, Natural Killer Cells: Methods and Protocols is a valuable resource for researchers who not only want to understand mechanisms that govern NK cell behavior and diversity, but also for those who want to understand how to systematically evaluate NK cells for adoptive immunotherapy applications.
Natural killer (NK) cells have been at the forefront of immunology for two decades. During that time, a great amount of information about these cells has been obtained. They are important in antiinfectious and antitumoral defense and shape the adaptive immune response. In addition, they can act as immunoregulatory cells. In recent years, the therapeutic potential of NK cells in cancer immunotherapy has become increasingly evident. This book describes in detail current knowledge about NK cells and covers a broad range of NK cell-related topics, including those that are not frequently reviewed, e.g. NK cells and allergy or NK cells and skin diseases.
Natural killer (NK) cells are crucial components of the innate immune system and play critical roles in host immunity against viral infections and cancer. NK cells' activity is controlled by the interaction of a wide range of receptors expressed on their surfaces with cell surface ligands. Opposite signals delivered by inhibitory and activating receptors tightly regulate NK cells' cytotoxicity. Natural killer cells can discriminate between normal and cancer cells. NK cells are known to directly recognize and kill malignant cells or induce apoptosis. However, tumor cells have the ability to evade those attacks. The main mechanisms involve the lack of expression or downregulation of the expression of major histocompatibility complex (MHC) class I molecules and secretion of soluble NKG2D ligands by tumor cells. Furthermore, tumors harbor a population of cancer stem cells (CSCs), which can drive tumor progression and therapeutical resistance. This chapter highlights the roles of NK cells in tumor immunosurveillance and their applications for cancer immunotherapy. NK cell biology and function as well as the role of their receptor interactions will be described. We will discuss the therapeutic applications of NK cells in cancer and NK cells targeting CSCs as a promising strategy for cancer therapy.
Recent advances in understanding of fundamental immunology have created new insights into the dynamic interactions between tumors and the immune system. This includes new understanding of T- and B-cell interaction, immune inhibitory mechanisms including the biology of T regulatory cells, myeloid suppressor cells, and dendritic cell subsets. Enhanced understanding of mechanisms underlying T-cell anergy such as arginine deprivation, immunosuppressive cytokines, defective innate and interferon response pathways, and NKG2D downregulation have all provided new insight into suppression of anti-tumor immunity and tumor evasion. In addition to emerging understanding of tumor evasion, new immune targets such as CTLA4 blockade, NK stimulatory receptors, manipulation of the antigen processing and presentation, cytokine and costimulatory responses all provide new possibilities for enhancing anti-tumor immunity even in tumors previously felt to be resistant to immune attack. Several of these strategies have already been realized in the clinic. The volume will explore evolving paradigms in antigen presentation, dendritic cell biology, the innate response and immunosuppressive mechanisms, and emerging strategies for manipulation of the immune system for therapeutic benefit that have realized success in neuroblastoma, leukemia, melanoma, lung cancer, and allogeneic transplantation. Early successes as well as failures will be highlighted to provide a snapshot of the state of clinical immunotherapy with an eye to future possibilities such as combination therapies, adoptive T-cell transfer, and the retargeting of immune cells via T-cell receptor engineering.
Cancer Immunotherapy Principles and Practice, from the Society of Immunotherapy of Cancer (SITC), is the authoritative reference on cancer immunobiology and the immunotherapy treatments that harness the immune system to combat malignant disease. Featuring five sections and over 50 chapters covering the Basic Principles of Tumor Immunology, Cancer Immunotherapy Targets and Classes, Immune Function in Cancer Patients, Disease Specific Treatments and Outcomes, and Regulatory Aspects of Cancer Immunotherapy, this book covers all major topics that have shaped the development of immunotherapy and propelled it to its current place at the forefront of cancer treatment innovation. This volume is a comprehensive resource for oncologists and fellows, immunologists, cancer researchers, and related practitioners seeking understanding of the basic science and clinical applications of cancer immunotherapy. As well as presenting the evidence for immune-based cancer treatment, it positions immunotherapy in the context of other available cancer treatments and provides data on response rates, risks, and toxicities across a variety of diseases. Filled with detailed tables, and instructive illustrations, as well as key points for quick reference, Cancer Immunotherapy Principles and Practice simplifies a challenging and dynamic subject. Key Features: Clearly summarizes the basic principles and research supporting cancer immunotherapy clinical translation Contains expert guidance and treatment strategies for all immunotherapy classes and agents, including cell-based therapies, monoclonal antibodies, cytokine therapies, checkpoint inhibitors, oncolytic viruses, adjuvant approaches, and treatment combinations Includes expert perspectives from leading authorities in the field Provides information on all FDA-approved immunotherapies, including clinical management and outcome data Discusses clinical aspects of immunotherapy for individual cancer types, including melanoma and other skin cancers, lung cancers, gynecologic cancers, gastrointestinal cancers, hematologic cancers, genitourinary cancers, head and neck cancers, sarcomas, brain and other CNS cancers, breast cancer, and pediatric malignancies. Explains regulatory aspects behind the development and approval of immunotherapy drugs Includes Online Access to the Digital Book
|Author||: Sandro Matosevic|
|Publisher||: Academic Press|
|Release Date||: 2020-12-01|
|ISBN 10||: 0128208805|
|Pages||: 200 pages|
Breaking Tolerance to Unresponsiveness to Immunotherapy by Natural Killer Cells presents chapters by leaders in translational natural killer cell research and bridges the gap between clinical need and basic science by presenting state-of-the-art knowledge on innate immunity and the challenges associated with translating it to practical adoptive immunotherapies. New approaches, such as the genetic engineering of NK cells and their combination with checkpoint blockade therapies are discussed among other potential interventions to improve natural killer cell functionality against targets. In addition, challenges, such as the difficulty in genetically modifying NK cells or a poor understanding of their effect on checkpoint inhibition are included. The book is a key reference and go-to resource for researchers and clinicians who want to understand the current limitations associated with bringing natural killer cell-based immunotherapies to the clinic. Discusses translational aspects from leaders in the field to facilitate readers’ understanding of clinical challenges Addresses important events that occur in patient tumor microenvironments as they pertain to NK cells and how they are, or can be, tackled to overcome immunosuppression of NK cells Focuses on immunometabolism by discussing the metabolic reprogramming that NK cells undergo in solid tumors, including hypoxia, adenosine and other metabolites