Download or read book Modulating T Cell Costimulation to Prevent Renal Allograft Rejection in Nonhuman Primates written by Lijun Song and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Organ transplantation is often the best therapeutic approach for end-stage organ failure. Graft rejection is the major obstacle to successful transplantation because transplantation is most frequently carried out between genetically distinct individuals. Transplanted tissues or organs are usually recognized by the immune system as foreign and are rapidly destructed without immune interventions. A series of approaches have thus been applied in clinic to inhibit the allogenic immune responses and in turn increase organ transplant acceptance. Immunosuppressive drugs are the key players in the "war" against immune cell-mediated rejection of allogenic transplants. Currently, the use of calcineurin inhibitors (CNIs) has dramatically decreased the risk of acute transplant rejection and improved the short-term outcomes of organ transplantation, but the long-term outcomes are still unsatisfied. One of the main reasons causing unsatisfied long-term outcomes is that current immunosuppressive drugs do not specifically target immune cells that cause transplant rejection. These immunosuppressive agents, especially CNIs, are the risk factors for late graft loss and death with functioning graft (DWFG) due to drug toxicity, over-immunosuppression, and other side-effects. Thus there is an urgent need for seeking novel therapies that can selectively eliminate the alloreactive immune responses while preserving the integrity of the remainder of the host immune system. It has been known that T cells play a central role in initiating allograft rejection. Full activation of T cells requires at least two collaborative but distinct signals. The first signal is generated by the interaction between T cell receptor (TCR) and MHC-peptide complex. The second signal, termed costimulatory signal, is delivered through the engagement of costimulatory receptors by their ligands. Importantly, TCR engagement in the absence of costimulatory signals can result in T cell anergy, a state of T cell unresponsiveness. Costimulatory molecules thus gain attention as potential therapeutic targets. Because these molecules are primary expressed on T cells and/or antigen-presenting cells, targeting costimulatory signaling pathway offers the oppertumities to modulate immune system in a more selective way relative to conventional immunosuppressive agents. To date, numerous costimulatory molecules have been identified and some have been tested as therapeutic targets in organ transplant models. CD28-CD80/86 and CD40-CD40L axis are two important and the most well known costimulatory signaling pathways. Belatacept, a variant of cytotoxic T lymphocyte antigen 4-immunoglobulin G (CTLA4-Ig) that blocks CD28-CD80/86 signaling pathway, is the only costimulation blocker to be approved for clinical use in organ transplantation. Compared to CNI-based regimen for kidney transplant recipients, belatacept-based regimens show similar patient and graft survival rate, superior graft function, and improved cardiovascular risk profile. However, belatacept is also associated with higher rates of acute rejection and posttransplant lymphoproliferative disorder (PTLD). Disruption of CD40-CD40L interaction with anti-CD40L mAbs has also been demonstrated to be a reliable approach for preventing acute rejection and for prolonging allograft survival. Unfortunately, unexpected thromboembolic complications in preclinical studies and clinical trials discontinued the development of anti-CD40L mAbs. The main objective of this thesis is to identify the optimal T cell costimulation blockers that can show improved safety and non-inferior efficacy in promoting allograft acceptance relative to current costimulatory blocking agents. Anti-CD40 mAbs are an alternative approach to block CD40-CD40L costimulatory pathway. CD40 is not involved in the stability of platelet thrombi and anti-CD40 mAbs are expected to not cause thromboembolic events. ASKP1240 is a novel fully human anti-CD40 mAb. In this study, the efficacy of ASKP1240 in the prevention of renal allograft rejection was evaluated in cynomolgus monkey kidney transplantation model. When ASKP1240 was administered alone, it dose-dependently reduced the incidence of acute rejection and prolonged renal allograft survival. Renal allograft acceptance was further improved in the monkey which received regiments using ASKP1240 combined with conventional immunosuppressive drugs tacrolimus (sub-therapeutic dose) or mycophenolate mofetil (MMF). Acute allograft rejection was totally eliminated in these animals and the kidney allograft median survival times (MST) of these groups were significantly longer than those of monotherapy groups. ASKP1240 administration did not induce cytokine release. This agent was well tolerated in monkey kidney transplant recipients during the 180-day treatment period. There were no obvious side effects including drug-related thromboembolic complications. Next, we tested the hypothesis that a CD86-selective variant of CTLA4-Ig might show non-inferior efficacy on the prevention of allograft rejection and prolongation of graft survival in comparison with belatacept. CD86 is the dominating ligand between the two natural ligands for CD28 in alloimmune response. Improvements in CD86 binding affinity of CTLA4-Igs confer increased immunosuppressive potency. A CD86-selective CTLA4-Ig variant may reach therapeutic levels of CD86 occupancy while occupies substantially less CD80 ligand than non-CD86-selective CTLA4-Igs. Preservation of CD80 signaling may be favoring to retain protective immunity and to improve safety of CTLA4-Ig therapy. This thesis investigated the effects of a novel CD86-selective CTLA4-Ig variant, ASP2409, on renal allograft rejection and survival in cynomolgus monkeys. ASP2409 possesses 14-fold higher in vitro CD86 binding affinity than belatacept and improved immunosuppressive potency. Compared to no-treatment control, low-dose (0.3 mg/kg) ASP2409 monotherapy significantly prolonged renal allograft survival (MST = 5 and 26 days, respectively) but did not decrease the incidence of acute rejection (8/8). The rate of acute renal allograft rejection was reduced in the group of high-dose ASP2409 monotherapy (2/7) and, correspondingly, a much longer MST (>91 days) was shown in this group. Combination therapy of low-dose ASP2409 and tacrolimus (sub-therapeutic dose) completely eliminated acute allograft rejection and notably prolonged renal allograft survival (MST >91 days). The MSTs of renal allografts in the animals receiving high-dose ASP2409-, belatacept-, and therapeutic dose tacrolimus-based immunosuppressive regimens were same (>91 days). High-dose ASP2409-based regimens exhibited better histopathological results than belatacept-based regimen. Furthermore, higher frequencies of FoxP3+ Tregs in renal allografts were observed in ASP2409- and belatacept-based regimens compared to tacrolimus-based regimen. ASP2409 was also demonstrated to be safe for animals with the doses to be tested. There were no serious side effects related to ASP2409 to be found in term of 91-day study. This study demonstrates that ASKP1240 is as effective as anti-CD40L mAbs on inhibition of acute rejection and prolongation of renal allograft survival, and do not cause thromboembolic complications. Previous studies indicated that CNIs could diminish the effects of anti-CD40L mAbs. In our study, ASKP1240 in combination with tacrolimus or MMF shows improved efficiency. Furthermore, the effects of ASP2409 on promoting renal allograft acceptance are not inferior to belatacept. These results collectively suggest that ASKP1240 and ASP2409 both are the promising immunosuppressive agents for solid organ transplantation.

Download or read book Greenfield s Surgery written by Michael W. Mulholland and published by Lippincott Williams & Wilkins. This book was released on 2016-11-15 with total page 5781 pages. Available in PDF, EPUB and Kindle. Book excerpt: Revised, updated, and enhanced from cover to cover, the Sixth Edition of Greenfield’s Surgery: Scientific Principles and Practice remains the gold standard text in the field of surgery. It reflects surgery’s rapid changes, new technologies, and innovative techniques, integrating new scientific knowledge with evolving changes in surgical care. Updates to this edition include new editors and contributors, and a greatly enhanced visual presentation. Balancing scientific advances with clinical practice, Greenfield’s Surgery is an invaluable resource for today’s residents and practicing surgeons.

Download or read book Immunology written by Richard Coico and published by John Wiley & Sons. This book was released on 2015-01-28 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immunology: A Short Course, 7th Edition introduces all the critical topics of modern immunology in a clear and succinct yet comprehensive fashion. The authors offer uniquely-balanced coverage of classical and contemporary approaches and basic and clinical aspects. The strength of Immunology: A Short Course is in providing a complete review of modern immunology without the burden of excessive data or theoretical discussions. Each chapter is divided into short, self-contained units that address key topics, illustrated by uniformly drawn, full-color illustrations and photographs. This new edition of Immunology: A Short Course: • Has been fully revised and updated, with a brand new art program to help reinforce learning • Includes a new chapter on Innate Immunity to reflect the growth in knowledge in this area • Highlights important therapeutic successes resulting from targeted antibody therapies • Includes end of chapter summaries and review questions, a companion website at www.wileyimmunology.com/coico featuring interactive flashcards, USMLE-style interactive MCQs, figures as PowerPoint slides, and case-based material to help understand clinical applications

Download or read book Kidney Transplantation Principles and Practice E Book written by Stuart J. Knechtle and published by Elsevier Health Sciences. This book was released on 2019-08-31 with total page 787 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offering practical guidance for all members of the transplant team, Kidney Transplantation, Principles and Practice, 8th Edition, provides the balanced, up-to-date information you need to achieve optimal outcomes for your patients. A global team of internationally renowned surgeons and nephrologists, many new to this edition, offers fresh perspectives on everything from applied science and surgical techniques to immunosuppressive methods, outcomes, risks, and medical considerations related to kidney transplantation, in both adults and children. - Offers state-of-the-art coverage of all areas of kidney transplantation such as preservation of kidneys; mechanisms of rejection and the induction of tolerance; techniques of laparoscopic live donor nephrectomy; and immunosuppression. - Contains up-to-date outcomes data and analysis of the evidence supporting current practice in the field. - Includes new information on desensitization and considerable new data on the clinical use of costimulation blockade. - Keeps you current with new chapters on kidney allocation policy that reflects the ethical and societal values of different countries and populations; and biomarkers of kidney injury and rejection, including the need for better monitoring tools to guide therapy and patient management. - Covers hot topics such as management of chronic allograft failure, the sensitized patient and antibody-mediated rejection, and paired exchange principles. - Features hundreds of superb illustrations to help you visualize key concepts and nuances of renal transplantation. - Provides dynamic visual guidance with new real-time video coverage of ultrasound-guided pancreas allograft biopsy; a new animation of calcineurin inhibitor mechanism of action animation; and videos that demonstrate the formation of an immune synapse, 3-D rotational images of immune synapses, an NK cell killing its target, peritoneal dialysis-catheter insertion techniques, laparoendoscopic single site (LESS) donor nephrectomy, and more. - Enhanced eBook version included with purchase, which allows you to access all of the text, figures, and references from the book on a variety of devices

Download or read book Tolerogenic Antigen Presenting Cells Modulating Unwanted Immune Response at Their Core written by John Isaacs and published by Frontiers Media SA. This book was released on 2019-12-27 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Frontiers in Transplantology written by Hesham Abdeldayem and published by BoD – Books on Demand. This book was released on 2016-09-07 with total page 312 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is addressed to researchers, practicing physicians, and surgeons in the field of organ transplantation, as well as the medical students, residents, and fellows. The topics covered include the religious concepts in organ transplantation, embryonic organ transplantation, tolerance, normothermic graft perfusion, pharmacogenetics of immunosuppressors, viral transmission in organ transplantation, pediatric and split-liver transplantation, portopulmonary hypertension, mechanical circulatory support, ex vivo lung perfusion, and ABO-incompatible kidney transplantation.

Download or read book Emerging Protein Biotherapeutics written by Iqbal S. Grewal and published by CRC Press. This book was released on 2009-06-26 with total page 372 pages. Available in PDF, EPUB and Kindle. Book excerpt: Given the speed at which antibody therapy is becoming readily accepted, a comprehensive industry guide is sorely needed. Written by leading international authorities, this book maintains an overall emphasis on various therapeutic approaches and applications and provides critical discussions on the most significant areas of research in biologics. It focuses on the applications of protein biologics in autoimmunity and inflammation, hematological malignancies, and solid tumors. Each chapter clearly presents the most informative and contemporary account of its subject available, making this an unrivaled reference source beneficial to those in both academia and biotechnology industries.

Download or read book Therapeutic Immunosuppression written by A.W. Thomson and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 516 pages. Available in PDF, EPUB and Kindle. Book excerpt: Therapeutic immunosuppression has very broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (e.g., rheumatoid arthritis), skin disease, and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. In addition, products of the biotechnology industry - monoclonal antibodies, cytokines, cytokine antagonists, and other products of genetic engineering that target key molecular pathways in disease pathogenesis - have either already made, or are on the verge of making an important impact on treatment. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. Gene therapy offers considerable promise for suppressing pathogenic processes in either transplantation or autoimmune disorders. The possibility of combining these important new advances to maximize benefit to the patient, and to minimize possible untoward effects (which are also given extensive coverage in this book), is one of the most exciting challenges of contemporary medicine. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area. Each chapter is contributed by one or more experts in the field. There was a need to bring this information together in a single volume, as much of the key recent developments have been dispersed throughout the biomedical literature, largely in specialized journals. Since, as in the past, important developments in immunosuppressive therapy in one branch of medicine (i.e. transplantation) are likely to benefit another (e.g., dermatology, rheumatology, gastroenterology), cross-disciplinary coverage of the mechanistic basis of the various therapeutic strategies in a single volume is likely to convey the potential of advances in therapy in the most coherent manner possible.

Download or read book Cumulated Index Medicus written by and published by . This book was released on 2000 with total page 1836 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Textbook of Organ Transplantation Set written by Allan D. Kirk and published by John Wiley & Sons. This book was released on 2014-07-21 with total page 1880 pages. Available in PDF, EPUB and Kindle. Book excerpt: Brought to you by the world’s leading transplantclinicians, Textbook of Organ Transplantation provides acomplete and comprehensive overview of modern transplantation inall its complexity, from basic science to gold-standard surgicaltechniques to post-operative care, and from likely outcomes toconsiderations for transplant program administration, bioethics andhealth policy. Beautifully produced in full color throughout, and with over 600high-quality illustrations, it successfully: Provides a solid overview of what transplantclinicians/surgeons do, and with topics presented in an order thata clinician will encounter them. Presents a holistic look at transplantation, foregrounding theinterrelationships between transplant team members and non-surgicalclinicians in the subspecialties relevant to pre- andpost-operative patient care, such as gastroenterology, nephrology,and cardiology. Offers a focused look at pediatric transplantation, andidentifies the ways in which it significantly differs fromtransplantation in adults. Includes coverage of essential non-clinical topics such astransplant program management and administration; research designand data collection; transplant policy and bioethical issues. Textbook of Organ Transplantation is the market-leadingand definitive transplantation reference work, and essentialreading for all transplant surgeons, transplant clinicians, programadministrators, basic and clinical investigators and any othermembers of the transplantation team responsible for the clinicalmanagement or scientific study of transplant patients.

Download or read book Therapeutic Immunosuppression written by Angus W. Thomson and published by Springer Science & Business Media. This book was released on 2001 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work has broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (for example, rheumatoid arthritis), skin disease and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area.

Download or read book Co signal Molecules in T Cell Activation written by Miyuki Azuma and published by Springer Nature. This book was released on 2019-11-22 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book equips young immunologists and health professionals with a clear understanding of the fundamental concepts and roles of co-signal molecules and in addition presents the latest information on co-stimulation. The first part of the book is devoted to co-signal molecules and the regulation of T cells. Following an initial overview, subsequent chapters examine each co-signal molecule in turn and discuss the mechanisms by which co-signal molecules regulate the different types of T cell. The second part covers various clinical applications, including in autoimmune disease, neurological disorders, transplantation, graft-versus-host disease, and cancer immunotherapy. To date, co-stimulation blockade and co-inhibition blockade have shown beneficial effects and many additional clinical trials targeting co-signal molecules are ongoing. The mechanisms underlying these successful treatments are explained and the future therapeutic potential in the aforementioned diseases is evaluated. Co-signal Molecules in T Cell Activation will be a valuable reference guide to co-stimulation for basic and clinical researchers in the fields of both immunology and pharmaceutical science.

Download or read book Adolescents with Chronic Kidney Disease written by Maha N. Haddad and published by Springer. This book was released on 2018-10-05 with total page 284 pages. Available in PDF, EPUB and Kindle. Book excerpt: End-stage renal disease is a devastating diagnosis to the patient, family and their care provider. This book covers all aspects of chronic kidney disease from a general description to its psychological impact on the adolescent and lastly its progression to end-stage and dialysis. It details the important aspects of the patient’s journey from diagnosis to their final destination including transplant and discussion of the medications used. It includes chapters on important etiologies of chronic kidney disease in adolescence, addressing the particular challenges a provider may be faced with in caring for this age group, and finally transition of their care to adult care providers. Written by experts in the field of pediatrics and nephrology Adolescents with Chronic Kidney Disease is the definitive resource in diagnosing and transitioning patients with chronic kidney disease.

Download or read book Progress of Allo and Xeno Transplantation Facilitating the Initial Xeno Kidney and Islet Clinical Trials written by Burcin Ekser and published by Frontiers Media SA. This book was released on 2022-10-11 with total page 216 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Primer on Transplantation written by American Society of Transplantation and published by John Wiley & Sons. This book was released on 2011-03-07 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Produced in association with the American Society of Transplantation, this new edition is full of practical advice for the next generation of transplant professionals. In addition to 5 organ-specific chapters: kidney, pancreas, heart, lung and liver, the book includes essential information on: immunobiology pharmacology donor management infectious complications pediatric transplantation general principles of patient management Fully updated and redesigned to make it even more user-friendly, the book now contains clinical vignettes, key point boxes, and self-assessment multiple choice questions in each chapter. Primer on Transplantation, Third Edition is an invaluable resource for all health professionals in the transplant team including trainees, residents, fellows, physicians, surgeons, nurses and transplant co-ordinators. Purchasing this book entitles you to access to the companion website: www.astprimer.com The website includes: Interactive Multiple-Choice Questions for each chapter Figures from the book as Powerpoints for downloading All chapters online

Download or read book Allergens and Allergen Immunotherapy Second Edition written by Richard F. Lockey and published by CRC Press. This book was released on 1998-09-30 with total page 831 pages. Available in PDF, EPUB and Kindle. Book excerpt: Researchers and clinicians relate their experience with immunotherapy using antigens, which has remained important throughout the enormous advances in immunology over the past 30 years. Among the topics are a historical perspective, outdoor and indoor allergens, venoms, the preparation and administration of extracts, and reactions and other adverse effects. Annotation copyrighted by Book News, Inc., Portland, OR

Download or read book The Science of Reconstructive Transplantation written by Gerald Brandacher and published by Humana Press. This book was released on 2015-05-13 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents a comprehensive overview of the latest advances in basic and translational research in the field of reconstructive transplantation and its potential therapeutic implications. Dr. Thomas E. Starzl and Dr. Raimund Margreiter, both pioneers in the field of transplantation, have written the foreword for the book. The volume spans such topics as skin rejection, immune monitoring, stem cell-based immunomodulatory strategies, costimulatory blockade, tolerance induction, chronic rejection, ischemia reperfusion injury, nerve regeneration, cortical reintegration, and small and large animal models for reconstructive transplantation. The book is intended for biomedical researchers and basic scientists in the field of reconstructive transplantation, transplant immunology and regenerative medicine, as well as clinicians, surgeons and multidisciplinary specialists, who are practicing or interested in this novel and exciting field. Postgraduate fellows and students will also find it a valuable reference.