Chimeric Antigen Receptor T-Cell Therapies for Cancer

From patient referral to post-therapy management, Chimeric Antigen Receptor (CAR) T-Cell Therapies for Cancer: A Practical Guide presents a comprehensive view of CAR modified T-cells in a concise and practical format. Providing authoritative guidance on the implementation and management of CAR T-cell therapy from Drs. Daniel W. Lee and Nirali N. Shah, this clinical resource keeps you up to date on the latest developments in this rapidly evolving area. Covers all clinical aspects, including patient referral, toxicities management, comorbidities, bridging therapy, post-CAR monitoring, and multidisciplinary approaches to supportive care. Includes key topics on associated toxicities such as predictive biomarkers, infections, and multidisciplinary approaches to supportive care. Presents current knowledge on FDA approved CAR T-cell products as well as developments on the horizon. Editors and authors represent leading investigators in academia and worldwide pioneers of CAR therapy.

Basics of Chimeric Antigen Receptor (CAR) Immunotherapy presents the latest on how T cell adoptive immunotherapy has progressed in its ultimate goal of curing metastatic malignant cancers. Recent clinical data obtained with checkpoint receptor blockade inhibitors and chimeric antigen receptor (CAR) therapy has been especially promising, thus generating renewed hope that we may be on the verge of finally curing cancer. Over the years, huge progress has been made in controlling several stage IV metastasized cancers through the clinical application of checkpoint receptor inhibitory drugs and CAR-Therapy that has seen unprecedented interest in the immunotherapy field. Presents the first book to provide a basic understanding of chimeric antigen receptor (CARs) design, production and clinical application protocols Provides unique authority as the editor has worked directly with CARs Discusses the challenges encountered in actual clinical trials and how these challenges can be overcome Includes a full chapter on various challenges researchers should expect to encounter in the CAR-therapy field

This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.

Stereotactic body radiation therapy (SBRT) has emerged as an important innovative treatment for various primary and metastatic cancers. This book provides a comprehensive and up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. It will serve as a detailed resource for this rapidly developing treatment modality. The organ sites covered include lung, liver, spine, pancreas, prostate, adrenal, head and neck, and female reproductive tract. Retrospective studies and prospective clinical trials on SBRT for various organ sites from around the world are examined, and toxicities and normal tissue constraints are discussed. This book features unique insights from world-renowned experts in SBRT from North America, Asia, and Europe. It will be necessary reading for radiation oncologists, radiation oncology residents and fellows, medical physicists, medical physics residents, medical oncologists, surgical oncologists, and cancer scientists.

Chimeric antigen receptor (CAR) T cells are genetically engineered immune cells that can seek out and destroy cancer cells. The results from their use in cancer immunotherapy have been very promising, but treatment is often associated with frequent, serious short-term toxicities. 'Fast Facts: CAR-T Therapy' explains what CAR T cells are and how they were developed, discusses the results of clinical trials and the management of toxicities, and outlines future improvements and applications. It is ideal reading for any healthcare professional wanting to know more about this exciting therapeutic field. Table of Contents: • CAR T cells • Clinical application • Practical aspects • Future directions

This volume provides comprehensive methods from expert scientists working in the Chimeric Antigen Receptor T Cell (CAR-T Cell) field. Chapters guide readers through the state-of-art of CAR-T cell technology, CAR design and vector production, CAR-T cell generation and manufacturing, CAR-T cell characterization, and quality control. Written in the highly successful Methods in Molecular Biology series format, 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. Authoritative and cutting-edge, Chimeric Antigen Receptor T Cells: Development and Production aims to be useful in the production of CAR-T cells, especially for therapeutic purposes.

This is a book about using the best evidence to inform treatmentdecisions for people with cancer. It is written by oncologists foroncologists, using examples throughout to illustrate key points.The book starts off with a "toolbox" section, written in a waywhich will help those relatively new to the principles ofevidence-based oncology to understand the key issues, and equipthem with the basics of how to tell a good study from a bad one.The majority of the book then deals with an evidence-based summaryof the common and important cancers in a structured and easy toread format around common patient scenarios and frequently askedquestions. Whilst most of the evidence is based on randomisedcontrolled trials, other studies are cited where appropriate egwhen discussing adverse events. The unique accompanying bookwebsite will contain updates of new chapters and studies as theybecome available. Written by leading world figures in the evidence-basedmovement Includes free CD-ROM with PC eBook and sample PDA chapter Methodology of reviewing and appraising evidence discussed inthe context of cancer management Clinical sections covering prevention and screening Chapters on treatment of the individual major cancers reviewthe current best available evidence to most frequently askedquestions Rigorously structured explicit searches, evidence of efficacyand harms, plus comment around clinical scenarios Free-access update website keeping the text current and live:www.evidbasedoncology.com

Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. Introduces the MSC-exosome mediated cell-cell communication Covers the major functional benefits in current MSC-derived exosome studies Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies

Part I- Understanding Cancer Immunotherapy: A brief Review. Immunotherapy, also called biologic therapy, is a type of cancer treatment that boosts the body's natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function. Immunotherapy may work by: Stopping or slowing the growth of cancer cells Stopping cancer from spreading to other parts of the body Helping the immune system work better at destroying cancer cells There are several types of immunotherapy, including: Monoclonal antibodies and tumor-agnostic therapies Non-specific immunotherapies Oncolytic virus therapy T-cell therapy Cancer vaccines Part II- “What is Chimeric Antigen Receptor (CAR) T- Cell Therapy?” An Emerging Cancer Treatment Modality. Chimeric antigen receptor (CAR) T-cell therapy is an emerging cancer treatment modality in which the patients’ own immune cells are collected, genetically engineered to recognize a tumor-related target, expanded in vitro, and then reinfused to produce responses and prevent progression in a variety of malignancies (ie, adoptive cell transfer) Several types of adoptive cell transfer(ACT) are under investigation, but CAR T-cell therapy is the first to enter clinical practice. Like other technologies, CAR-T cell therapy has undergone a long development process in the past. Chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving. At present, CAR-T cell therapy is developing rapidly, and many clinical trials have been established on a global scale, which has great commercial potential. I have endeavored to compile this E- Booklet into Two Parts i.e. Part I & Part II for better understanding of Chimeric antigen receptor (CAR) T-cell therapy, an emerging cancer treatment modality. In Part I, an effort has been made to describe Cancer Immunotherapy briefly whereas in Part II know about of CAR T-Cell Therapy-the first to enter clinical practice- has been embodied. Further it is attempted to describe toxicity of CAR-T cell therapy briefly and future development and opportunities for immunotherapy. …Dr. H. K. Saboowala. M.B.(Bom) .M.R.S.H.(London)

Leading authorities provide a valuable account of the clinical and labratory issue related to allogeneic stem cell transplantation. Key chapters feature such topics as the selection of optimal inrelated allogeneic grafts for patients with hematologic malignancies; issues related to stem cell mobilization in normal donors; allogeneic peripheral blood cell vs marrow-derived transplantation; umbilical cord blood as a new stem cell source; kinetics of immune reconstitution post allogeneic transplantation; the role of allogeneic transplantation in breast cancer, and; the application of mini-conditioning in allogeneic grafting. The book will serve as a guide in development of innovative clinical and labratory inquiry in the field of allogeneic transplantation for all clinicians and labratory investigators focused on hematopoetic stem cells and immune biology research.

In this book, leading experts in cancer immunotherapy join forces to provide a comprehensive guide that sets out the main principles of oncoimmunology and examines the latest advances and their implications for clinical practice, focusing in particular on drugs with FDA/EMA approvals and breakthrough status. The aim is to deliver a landmark educational tool that will serve as the definitive reference for MD and PhD students while also meeting the needs of established researchers and healthcare professionals. Immunotherapy-based approaches are now inducing long-lasting clinical responses across multiple histological types of neoplasia, in previously difficult-to-treat metastatic cancers. The future challenges for oncologists are to understand and exploit the cellular and molecular components of complex immune networks, to optimize combinatorial regimens, to avoid immune-related side effects, and to plan immunomonitoring studies for biomarker discovery. The editors hope that this book will guide future and established health professionals toward the effective application of cancer immunology and immunotherapy and contribute significantly to further progress in the field.

Get a quick, expert overview of hematologic and non-hematologic malignancies for which hematopoietic cell transplantation is a treatment option. Drs. Qaiser Bashir and Mehdi Hamadani provide easy-to-find information on basic science of hematopoietic cell transplantation, pharmacology, workflows and procedures, possible complications and side effects, in addition to the role of HCT in conjunction with clinical cellular therapy. Discusses high-dose chemotherapeutic regimens and radiation therapy, patient and donor selection and workup, as well as other key aspects of hematopoietic cell transplantation. Includes practical information on complications, infectious disease, and special populations such as patients with HIV infection. Consolidates today’s available information in this fast-changing area into one convenient resource.

Chimeric antigen receptor (CAR) T cell therapies for leukemia (e.g. tisagenlecleucel) and lymphoma (e.g. axicabtagene ciloleucel) have recently received regulatory approval in the United States. Phase I/II trials have demonstrated complete remission of refractory or relapsed tumors in 50% - 94% patients. However, the clinical successes of engineered T cells for the treatment of solid malignancies have thus far been few and far between. Furthermore, several instances of severe and lethal toxicities have arisen due to on-target, off-tumor recognition of antigen by T cell products. Recent advances in phase I trials for solid tumors, as well as in pre-clinical models, have revealed several variables that will be important to consider for the successful use of CAR-T cells in treating solid tumors. These variables include (i) regional versus systemic delivery; (ii) scFv versus ligand interactions; (iii) antigen loss versus escape; (iv) epitope spreading and (v) checkpoint expression on immune cells or tumor cells. Also, there remains outstanding mechanistic questions related to why differences exist in the persistence and tonic signaling of second-generation CD28 versus 4-1BB co-stimulated CAR-T cells. In addition, we are now learning the roles of lympho-depleting regimens (and associated toxicities) in modifying the persistence of engineered T cell therapies. A more comprehensive view of CAR-T cell strategies and important advances, both of pre-clinical and clinical evaluations, in solid tumors is necessary to drive these therapies forward.

From patient referral to post-therapy management, Chimeric Antigen Receptor (CAR) T-Cell Therapies for Cancer: A Practical Guide presents a comprehensive view of CAR modified T-cells in a concise and practical format. Providing authoritative guidance on the implementation and management of CAR T-cell therapy from Drs. Daniel W. Lee and Nirali N. Shah, this clinical resource keeps you up to date on the latest developments in this rapidly evolving area. Covers all clinical aspects, including patient referral, toxicities management, comorbidities, bridging therapy, post-CAR monitoring, and multidisciplinary approaches to supportive care. Includes key topics on associated toxicities such as predictive biomarkers, infections, and multidisciplinary approaches to supportive care. Presents current knowledge on FDA approved CAR T-cell products as well as developments on the horizon. Editors and authors represent leading investigators in academia and worldwide pioneers of CAR therapy.

Immunological Concepts in Transfusion Medicine provides a thorough discussion of the immune aspects of blood component transfusion, with in-depth information on the intricacies of immune responses to blood components and the immune processes that may be initiated in response to blood exposure. Written to increase knowledge and awareness of immune challenges such as alloimmunization and transfusion-related acute lung injury, this title bridges current basic scientific discoveries and the potential effects seen in blood recipients. Complies the knowledge and expertise of Dr. Robert Maitta, an expert in immune responses and antibody function/structure studies. Helps clinicians in the daily practice of caring for patients in need of transfusion support, as well as physicians in training when considering utilizing blood transfusions in a limited scope or in the setting of massive transfusion. Includes an immunology primer as an introduction to in-depth chapters covering allergic immune reactions to blood components, transfusion-related immunomodulation, fetal and neonatal alloimmune thrombocytopenia and neonatal neuthropenia, complications of haploidentical and mismatched HSC transplantation, chimeric antibody receptor therapies, and much more. Consolidates today’s available information on this timely topic into a single, convenient resource.

This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.

Second Generation Cell and Gene-Based Therapies: Biological Advances, Clinical Outcomes, and Strategies for Capitalisation serves as the only volume to the market to bridge basic science, clinical therapy, technology development, and business in the field of cellular therapy/cytotherapy. After more than two decades of painstaking fundamental research, the concept of therapeutic cells (stem cells, genes, etc.), beyond the concept of vaccines, is reaching clinical trial, with mounting confidence in the safety and efficacy of these products. Nonetheless, numerous incremental technical advances remain to be achieved. Thus, this volume highlights the possible R&D paths, which will ultimately facilitate clinical delivery of cutting edge curative products. The next waves of innovation are reviewed in depth for hematopoietic stem cells, mesenchymal stem cells, tissue engineering, CAR-T cells, and cells of the immune system, as well as for enabling technologies such as gene and genome editing. Additionally, deep dives in product fundamentals, history of science, pathobiology of diseases, scientific and technological bases, and financing and technology adoption constraints are taken to unravel what will shape the cytotherapy industry to the horizon 2025 and beyond. The outcome is not simply a scientific book, but a global perspective on the nascent field combining science, business, and strategic fundamentals. Helps readers learn about the most current trends in cell-based therapy, their overall effectiveness from a clinical prospective, and how the industry is moving therapies forward for capitalization "Perspectives" section at the end of each chapter summarizes key learnings, hypotheses, and objectives highlighted and combines scientific and business insights Edited and authored by scientists representing both basic and clinical research and industry, presenting a complete story of the current state and future promise of cellular therapies

Cancer Cell Signaling: Methods and Protocols, Second Edition brings together the most recent advances in cancer cell signaling knowledge along with recent progress in the development of novel strategies and experimental cell models to study human cancer. Opening with a section on targeting cancer cell metabolism as an anticancer strategy, this detailed volume continues with parts describing protocols to study epigenetic control of cancer, protocols to study cancer metastasis, as well as two new techniques for cancer study. Written for the highly successful Methods in Molecular Biology series, chapters include introductions for 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. Authoritative and timely, Cancer Cell Signaling: Methods and Protocols, Second Edition is an ideal guide to the techniques that will aid researchers in exploiting our current knowledge in order to make a profound impact in cancer prevention and treatment.

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.