Experts from a variety of areas compare and discuss IL-6 and LIF in order to provide a new understanding of their modes of action, the significance of their polyfunctionalization--why the body chooses to use one molecule to regulate various cell types--and their functional overlap. Covers such topics as actions of IL-6 and LIF on lymphoid populations, on megakaryocyte and platelet production, on bone metabolism, their effects on leukemic cells and much more. Includes contributions from researchers working on a variety of cell types and organ systems along with potential clinical applications regarding these two factors.
Presents timely and authoritative information on the development of precision cancer therapies as applied to hematologic malignancies The Precision Cancer Therapies series focuses on how to understand and translate fundamental basic science into information that can be directly applied to patients to advance care. Each volume of the series integrates the relevant biological concepts and principles necessary for translating this science to practitioners of this science. Precision Cancer Therapies, Volume Two, focuses on sophisticated immunotherapies targeting cancers affecting the blood, bone marrow, and lymph nodes. Edited and authored by the foremost authorities in the field, this comprehensive reference text covers targeting of cell surface receptors, antibody-drug conjugates (ADC), targeting immune checkpoint, targeting macrophages, EBV-directed immunotherapies, tumor-associated antigens (TAA), and chimeric antigen receptor T-cells (CAR-T). Divided into nine sections, Volume Two includes an overview of the history of immunotherapy development in cancer, as well as a concluding section addressing the mechanistic basis and role of immunomodulatory drugs, analytical tools to quantitate immune-mediated effects, and other topics in immunotherapy. Chapters on specific therapeutics or therapeutic classes include a basic explanation of the underlying pathway and target, the pharmacology of the drug/class, relevant preclinical and clinical data, and discussion of clinical management and potential predictive biomarkers of response. This book also: Delivers a definitive, state-of-the-art review of the relevant biology and its importance in the broader context of cancer biology Focuses on agents that mediate cell killing in lymphoma through a variety of immunologic mechanisms Covers FDA-approved drugs and their indications, as well as drugs currently in development Provides information on monotherapy and combination therapy, summary tables of trials, and discussion of toxicity and efficacy Includes boxed sections highlighting major unique points about the information in the chapter Precision Cancer Therapies, Volume Two: Immunologic Approaches for the Treatment of Lymphoid Malignancies, From Concept to Practice is an indispensable resource for medical, scientific, and allied medical professionals, advanced students, and interested general readers with background knowledge in the subject.
This volume illustrates the salient aspects of cancer biology relevant to the successful implementation of immunotherapy. Topics include enhancement of antigen-specific immune responses by anti-cancer vaccines, modulation of the function of T cells within the tumor microenvironment, and the effects of genetic, epigenetic, developmental, and environmental determinants on T cell function. Other topics covered include the ex vivo expansion of T or other immune cells and their genetic modification or reprogramming to increase their ability to survive and expand when adoptively transferred back to the patients. Specific attention is devoted to the genetic manipulation of T cells through the introduction of re-directed T cell receptors, chimeric antibody receptors, and other genetic manipulation aimed at improving their effectiveness as anti-cancer agents. Furthermore, the revolutionary role of checkpoint inhibitors and their potential in combination with other immunotherapeutic approaches or with standard chemo and radiation therapy are extensively discussed.
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Dissection of the specificity of host immune responses following infection with Mycobacterium tuberculosis is essential for designing effective vaccination and diagnostic biomarkers as well as for better understanding of immunopathogenesis of active tuberculosis. The articles in this volume of the Topics in Microbial Immunology review the significance of this area of research from both experimental models and clinical surveys. This includes T cell recognition of MHC permissive epitopes, use of algorithms for genome-based prediction of immunodominant epitopes, evaluation of candidate antigens/epitopes and adjuvants for vaccination and immunodiagnosis. Future research strategies indicate the need for better understanding of the relationship between epitope specificity and the phenotype of responding T cells and search for biomarkers with a capacity to discriminate and predict the change from latent infection to active disease. These research avenues have important potentials for improving the prevention and control of tuberculosis.
Historically, the field of hematopoietic growth factor research began with the work of Carnot and Deflandre-in 1906 they suggested that the rate of erythropoiesis is regulated by a humoral factor found in the blood, namely, erythropoietin. From this comparatively early start, accelerating progress has been made in erythropoietin research, which demon strates the general trends in this field of study. Erythropoietin was purified to homogeneity by 1977 (from enormous quantities of urine from aplastic anemia patients). Subsequently, the gene for erythropoietin has been cloned (1985), and massive quantities of this growth factor have been produced for clinical trials (late 1980s onward). Erythropoietin has become established as a pharmaceutical product of great value in the treatment of a number of diseases, most notably chronic renal failure. Once the ligand had been cloned, interest turned to the erythropoietin receptor, which was cloned in 1989. Since then, structure/ function studies have been performed on receptor mutants, cellular signaling events down stream from the occupied receptor have been identified, and the specific producer cell types and molecular stimuli for erythropoietin production have been thoroughly investigated, as has the regulation of erythropoietin gene transcription. This schedule of events since the 1970s typifies that seen for a number of hematopoietic growth factors. Along the way, the hematopoietic growth factors have been recognized as members of the cytokine family of signaling molecules that are important in a number of different physiological and patholog ical situations (see below).
COVID-19 is a recently emerged infectious disease caused by the novel coronavirus SARS-CoV-2. The immune system has a primary role in pathogen elimination and a rapid and effective response can limit disease severity. In this context, T cells play the major role in cell mediated adaptive immune response. The protective role of CD4+ and CD8+ T cells has been inferred from studies on patients who recovered from SARS and MERS and accumulating data are now showing their relevance in SARS-CoV-2 infection. Moreover, memory T cells induced by previous pathogens can shape the susceptibility to, and the clinical severity of other infections, but the complete picture has yet to be elucidated. If the virus is not rapidly eliminated, COVID-19 may progress towards a secondary inflammatory phase that is directly responsible for a worsening in clinical symptoms and immune system impairment. Besides marked lymphopenia, COVID-19 patients’ T cell compartment displays several alterations involving different subpopulations of T cells in terms of phenotype, metabolic profile and functionality.
Tuberculosis (TB) remains the prime bacterial infection worldwide with 10.4 million infections and a death toll of 1.7 million people in 2016 according to WHO statistics. Tuberculosis is caused by members of the Mycobacterium tuberculosis complex, facultative intracellular bacteria able to thrive within otherwise potent innate defense cells, the macrophages. In a world of increasing numbers of infections with drug resistant M. tuberculosis strains, the daunting race between developing new therapeutics and emerging resistant strains will hardly produce a winner. This cycle can only be broken by enhancing population wide immune control through a better vaccine as the only one currently in use, M. bovis Bacillus Calmette Guerin (BCG). The protective efficacy of BCG against pulmonary tuberculosis in all age groups is dissatisfying and geographically highly diverse with the tropical areas showing the lowest efficacy rates. Despite worldwide vaccination coverage, the impact of BCG on the steep decrease of tuberculosis incidence rates in the developed world seems therefore questionable and can rather be attributed to improved social, housing and nutritional conditions, better health care, surveillance and treatment systems. The last 15 years saw tremendous efforts to improve vaccination strategies against tuberculosis. Different paths of vaccine approaches were followed including genetically improved BCG strains, attenuated M. tuberculosis variants, recombinant viral vectors and subunit vaccine candidates combined with novel more potent adjuvants. With the first novel vaccine candidates being evaluated in clinical phases II and III and initial results chastening the expectations, a critical reassessment of all candidates is inevitable. Here, we assembled experts to review and assess the current status of novel anti-tuberculosis vaccine candidates, their efficacy and prospects for implementation as well as the pitfalls and possible measures for improvement.
