Intratumoral Dendritic Cell Vaccine Reprograms the Tumor Microenvironment and Enhances the Efficacy of Immune Checkpoint Blockade in Non-Small Cell Lung Cancer PDF Download
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Author: Raymond John S Lim
Publisher:
ISBN:
Category :
Languages : en
Pages : 126
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Book Description
Lung cancer remains the most common cause of cancer death worldwide with approximately 85% of patients having non-small cell lung cancer (NSCLC). Checkpoint blockade immunotherapy has evolved the current treatment landscape with robust and durable responses in approximately 20% of patients with progressive, locally advanced, or metastatic NSCLC, as well as in treatment-naïve advanced disease. Inefficient tumor antigen presentation, diminished T cell infiltration into tumor and LKB1-inactivating mutations contribute to the mechanisms of resistance to programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) blockade in NSCLC. One approach to overcome this immunosuppressive tumor microenvironment (TME) is to utilize in situ vaccination with gene-modified functional antigen presenting cells (APCs) to enhance tumor antigen presentation and promote tumor-specific T cell activation. Here I address two potential therapies: 1) CCL21-genetically engineered dendritic cells (CCL21-DC) and 2) CXCL9/10-genetically engineered dendritic cells (CXCL9/10-DC), which are shown to remodel the tumor immune microenvironment and promote an anti-tumor immune response. In addition, the pre-clinical studies detailed here investigate the mechanisms of how these potential therapies can potentiate checkpoint blockade immunotherapy. These preclinical models serve as a platform to enhance our understanding of the molecular mechanisms of response and resistance to immunotherapy. In addition, these studies provide insights to anti-tumor immunity mediated by in situ DC vaccination and may in turn facilitate the improvement of novel vaccine therapies. The final chapter addresses the pressing need for the development of innovative approaches to detect and intercept lung cancer at its earliest stages of development. Using spatial multiplex immunofluorescence, this chapter highlights the efforts to understand the immune landscape in the tumor microenvironment associated with early-stage lung carcinogenesis and provides further understanding of the mechanism of lung cancer evolution. Research focusing on the development of novel strategies for cancer interception prior to the progression to advanced stages will potentially lead to a paradigm shift in the treatment of lung cancer and have a major impact on clinical outcomes.
Author: Raymond John S Lim
Publisher:
ISBN:
Category :
Languages : en
Pages : 126
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Book Description
Lung cancer remains the most common cause of cancer death worldwide with approximately 85% of patients having non-small cell lung cancer (NSCLC). Checkpoint blockade immunotherapy has evolved the current treatment landscape with robust and durable responses in approximately 20% of patients with progressive, locally advanced, or metastatic NSCLC, as well as in treatment-naïve advanced disease. Inefficient tumor antigen presentation, diminished T cell infiltration into tumor and LKB1-inactivating mutations contribute to the mechanisms of resistance to programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1) blockade in NSCLC. One approach to overcome this immunosuppressive tumor microenvironment (TME) is to utilize in situ vaccination with gene-modified functional antigen presenting cells (APCs) to enhance tumor antigen presentation and promote tumor-specific T cell activation. Here I address two potential therapies: 1) CCL21-genetically engineered dendritic cells (CCL21-DC) and 2) CXCL9/10-genetically engineered dendritic cells (CXCL9/10-DC), which are shown to remodel the tumor immune microenvironment and promote an anti-tumor immune response. In addition, the pre-clinical studies detailed here investigate the mechanisms of how these potential therapies can potentiate checkpoint blockade immunotherapy. These preclinical models serve as a platform to enhance our understanding of the molecular mechanisms of response and resistance to immunotherapy. In addition, these studies provide insights to anti-tumor immunity mediated by in situ DC vaccination and may in turn facilitate the improvement of novel vaccine therapies. The final chapter addresses the pressing need for the development of innovative approaches to detect and intercept lung cancer at its earliest stages of development. Using spatial multiplex immunofluorescence, this chapter highlights the efforts to understand the immune landscape in the tumor microenvironment associated with early-stage lung carcinogenesis and provides further understanding of the mechanism of lung cancer evolution. Research focusing on the development of novel strategies for cancer interception prior to the progression to advanced stages will potentially lead to a paradigm shift in the treatment of lung cancer and have a major impact on clinical outcomes.
Author: Jessica Dal Col
Publisher: Frontiers Media SA
ISBN: 2889637263
Category :
Languages : en
Pages : 125
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Book Description
Author: Sergei Kusmartsev
Publisher: Frontiers Media SA
ISBN: 2889714985
Category : Medical
Languages : en
Pages : 202
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Book Description
Author: An M. T. Van Nuffel
Publisher: Frontiers Media SA
ISBN: 2889631605
Category :
Languages : en
Pages : 196
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Book Description
Although cancer vaccines have yielded promising results both in vitro and in animal models, their translation into clinical application has not been very successful so far. Through the success of immune checkpoint inhibitors, the tumor immunotherapy field revived and led to important new insights. A better understanding of the functional capacity of different dendritic cell (DC) subsets and the immunogenicity of tumor antigens, more particularly of neoantigens, have important implications for the improvement of cancer vaccines. These insights can guide the development of novel strategies, to enhance the clinical utility of cancer vaccines. The aim of this Research Topic is therefore to provide a comprehensive overview of current issues regarding cancer vaccine development with an emphasis on novel approaches toward enhancing their efficacy.
Author: Paul D. Rennert
Publisher: Springer
ISBN: 3319298275
Category : Medical
Languages : en
Pages : 285
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Book Description
Cancer care is undergoing a radical transformation as novel technologies are directed toward new treatments and personalized medicine. The most dramatic advances in the treatment of cancer have come from therapeutics that augment the immune response to tumors. The immune checkpoint inhibitors are the best-known and most highly advanced examples of Immune Therapeutics targeting tumor cells and include approved antibody drugs directed at the cell surface proteins CTLA4 and PD-1. These are now considered foundational treatments for several solid tumor indications, and that list of indications is growing quickly. More broadly, antibodies have become workhorse molecules across the entire immunotherapy landscape. Antibodies to novel targets modulate the activity of diverse immune cell regulatory proteins. Engineered antibodies can induce tumor cell death or expose tumor cells to poisonous toxins (ADCC and ADC, respectively). Bi-specific antibodies can engage multiple tumor targets simultaneously, or can redirect lymphocytes to attack tumor cells. The antigen-binding domains within antibodies can be spliced onto cell stimulatory domains and transduced into T cells or NK cells, creating remarkable tumor-specific cellular therapeutics (CAR-T, CAR-NK). Beyond antibody-based therapies there are highly diverse and differentiated technology tool kits being applied to immunotherapy. Small molecule drugs are being developed to attack the tumor microenvironment, novel tumor vaccine approaches are showing great promise, patient lymphocytes are being isolated, expanded and reintroduced to patients, gene-editing techniques are becoming widely deployed, and a vast number of new tumor targets, and mutated tumor proteins (neoantigens), are being discovered. The past decade has seen unprecedented success in the treatment of diverse cancers. The authors of this volume have been asked to not only review progress to date, but importantly, to look ahead, and anticipate the evolution of cancer treatment across diverse Immune Therapeutic approaches. Our hypothesis is that the advances we are seeing across the immunotherapy landscape will further evolve and synergize, leading us finally to outright cures for many cancers.
Author: Fumito Ito
Publisher: Elsevier Health Sciences
ISBN: 0323549500
Category : Medical
Languages : en
Pages : 400
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Book Description
Get a quick, expert overview of the latest clinical information and guidelines for cancer checkpoint inhibitors and their implications for specific types of cancers. This practical title by Drs. Fumito Ito and Marc Ernstoff synthesizes the most up-to-date research and clinical guidance available on immune checkpoint inhibitors and presents this information in a compact, easy-to-digest resource. It’s an ideal concise reference for trainee and practicing medical oncologists, as well as those in research. Discusses the current understanding of how to best harness the immune system against different types of cancer at various stages. Helps you translate current research and literature into practical information for daily practice. Presents information logically organized by disease site. Covers tumor immunology and biology; toxicities associated with immune checkpoint inhibitors; and future outlooks. Consolidates today’s available information on this timely topic into one convenient resource.
Author: Ashutosh Tiwari
Publisher: John Wiley & Sons
ISBN: 1118773683
Category : Technology & Engineering
Languages : en
Pages : 421
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Book Description
Offers a comprehensive and interdisciplinary view of cutting-edge research on advanced materials for healthcare technology and applications Advanced healthcare materials are attracting strong interest in fundamental as well as applied medical science and technology. This book summarizes the current state of knowledge in the field of advanced materials for functional therapeutics, point-of-care diagnostics, translational materials, and up-and-coming bioengineering devices. Advanced Healthcare Materials highlights the key features that enable the design of stimuli-responsive smart nanoparticles, novel biomaterials, and nano/micro devices for either diagnosis or therapy, or both, called theranostics. It also presents the latest advancements in healthcare materials and medical technology. The senior researchers from global knowledge centers have written topics including: State-of-the-art of biomaterials for human health Micro- and nanoparticles and their application in biosensors The role of immunoassays Stimuli-responsive smart nanoparticles Diagnosis and treatment of cancer Advanced materials for biomedical application and drug delivery Nanoparticles for diagnosis and/or treatment of Alzheimers disease Hierarchical modelling of elastic behavior of human dental tissue Biodegradable porous hydrogels Hydrogels in tissue engineering, drug delivery, and wound care Modified natural zeolites Supramolecular hydrogels based on cyclodextrin poly(pseudo)rotaxane Polyhydroxyalkanoate-based biomaterials Biomimetic molecularly imprinted polymers
Author: Laurence Zitvogel
Publisher: Springer
ISBN: 3319624318
Category : Medical
Languages : en
Pages : 700
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Book Description
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.
Author:
Publisher:
ISBN: 9789811532672
Category : Cancer
Languages : en
Pages : 657
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Book Description
This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.
Author: Yongsheng Li
Publisher: Springer
ISBN: 9789813367876
Category : Medical
Languages : en
Pages : 211
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Book Description
This book focuses on lipid metabolism in tumor immunity, covering the application of lipidomics in tumor immunity and all aspects of lipid metabolism in tumor microenvironment. During the progression of tumors, tumor cells and immune cells interact in a dynamic microenvironment. Targeting the immune system has a high potential for treating cancer. However, due to the high heterogeneity of the tumor microenvironment, only a small percentage of patients experience such clinical benefits of tumor immunotherapy. Therefore, understanding the tumor microenvironment is crucial for tumor immunity. Recently, lipid metabolism is an emerging research direction and contributes to cell survival and biofunctions in tumor microenvironment, which is of great interest and significance to be elucidated. This book provides the doctors, researchers, and scientists with a cutting-edge overview of the lipid metabolism and its role in tumor immunity. It also yields benefits for pharmaceutical companies regarding drug discovery.
