Dissecting the Mechanism of T Cell Tolerance for More Effective Breast Cancer Vaccine Development PDF Download
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Languages : en
Pages : 25
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Book Description
T cell tolerance to tumor-associated antigens is a significant barrier to immune based treatments of human cancers. One such tumor-associated antigen is the protooncogene HER-2/neu (neu) which is overexpressed in 35-40% of all human breast cancers. Although patients with neu expressing tumors develop antibody and T cell responses to this antigen, these responses are weak and unable to hinder tumor growth. Our work has focused on understanding these mechanisms of T cell tolerance using the neu-N transgenic mice that express the wild type rat neu cDNA under control of the MMTV promoter. Since neu is an endogenously expressed antigen, profound neu-specific immune tolerance exists in the neu-N mice. We have characterized the immunodominant T cell epitope of neu recognized by parental FVB/N mice, RNEU420-429. Studying T cell responses to this epitope has yielded important insights into the mechanisms of tolerance in the neu-N mice. Following a neu-targeted vaccine, 100% of FVE/N mice will activate T cells specific to RNEU420-429, whereas RNEU420-429-specific T cells are not activated in the neu-N mice. However, if vaccine is combined with immunomodulatory doses of chemotherapy in neu-N mice, RNEU420-420-specific are now activated in a subset of transgenic mice. Employing MHC tetramer technology, adoptive transfer of RNEU420.429-specific T cells, and T cell activation assays, we have begun to understand the mechanisms of tolerance that prevent the induction of protective immunity against tumors in the neu-N mice and ways to circumvent them. These findings are the basis for a Phase I Clinical Trial now underway at our institution.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 25
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Book Description
T cell tolerance to tumor-associated antigens is a significant barrier to immune based treatments of human cancers. One such tumor-associated antigen is the protooncogene HER-2/neu (neu) which is overexpressed in 35-40% of all human breast cancers. Although patients with neu expressing tumors develop antibody and T cell responses to this antigen, these responses are weak and unable to hinder tumor growth. Our work has focused on understanding these mechanisms of T cell tolerance using the neu-N transgenic mice that express the wild type rat neu cDNA under control of the MMTV promoter. Since neu is an endogenously expressed antigen, profound neu-specific immune tolerance exists in the neu-N mice. We have characterized the immunodominant T cell epitope of neu recognized by parental FVB/N mice, RNEU420-429. Studying T cell responses to this epitope has yielded important insights into the mechanisms of tolerance in the neu-N mice. Following a neu-targeted vaccine, 100% of FVE/N mice will activate T cells specific to RNEU420-429, whereas RNEU420-429-specific T cells are not activated in the neu-N mice. However, if vaccine is combined with immunomodulatory doses of chemotherapy in neu-N mice, RNEU420-420-specific are now activated in a subset of transgenic mice. Employing MHC tetramer technology, adoptive transfer of RNEU420.429-specific T cells, and T cell activation assays, we have begun to understand the mechanisms of tolerance that prevent the induction of protective immunity against tumors in the neu-N mice and ways to circumvent them. These findings are the basis for a Phase I Clinical Trial now underway at our institution.
Author:
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ISBN:
Category :
Languages : en
Pages : 0
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Book Description
T cell tolerance to tumor-associated antigens is a significant barrier to immune based treatments of human cancers. One such tumor-associated antigen is the proto-oncogene HER-2/neu (neu) which is overexpressed in 35-40% of all human breast cancers. Although patients with neu expressing tumors develop antibody and T cell responses to this antigen, these responses are weak and unable to hinder tumor growth. Our work has focused on understanding these mechanisms of T cell tolerance using the neu-N transgenic mice that express the wild type rat neu cDNA under control of the MMTV promoter. Since neu is an endogenously expressed antigen, profound neu-specific immune tolerance exists in the neu-N mice. We previously reported the immunodominant T cell epitope of neu recognized by parental FVB/N mice, RNEU420-429. We have investigated whether altering RNEU420-429 can generate a more immunogenic peptide that will result in better protection from a HER-2/neu expressing tumor in the neu-N mice. Also, using GFP-expressing RNEU420-429-specific T cells, we demonstrate that high avidity CTL cannot persist in the periphery of neu-N mice but do persist in the periphery of parental mice. Further studies are underway to understand the role other immune cells (such as CD4(+)CD25(+) regulatory T cells) play in CD8(+) T cell tolerance. This work to further understand the mechanisms of T cell tolerance in this cancer model should lead to even further improvements in vaccination strategy for cancer immunotherapies.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309169887
Category : Medical
Languages : en
Pages : 304
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Book Description
By two years of age, healthy infants in the United States can receive up to 20 vaccinations to protect against 11 diseases. Although most people know that vaccines effectively protect against serious infectious diseases, approximately one-quarter of parents in a recent survey believe that infants get more vaccines than are good for them, and that too many immunizations could overwhelm an infant's immune system. The Immunization Safety Review Committee reviewed the evidence regarding the hypothesis that multiple immunizations increase the risk for immune dysfunction. Specifically, the committee looked at evidence of potential biological mechanisms and at epidemiological evidence for or against causality related to risk for infections, the autoimmune disease type 1 diabetes, and allergic disorders.
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: Fritz H. Bach
Publisher: Wiley-Liss
ISBN:
Category : Medical
Languages : en
Pages : 432
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Book Description
Transplantation Immunology Edited by Fritz H. Bach, M.D., and Hugh Auchincloss, Jr., M.D. In recent years, transplantation immunology has evolved as a distinct field founded on the recognition that rejection of a transplanted organ or tissue is mediated by immune mechanisms in the host responding to antigens in the donor tissue. This book provides a comprehensive, up-to-date review of current knowledge regarding the specific immune mechanisms which can cause recipients to reject clinical transplants. The text is divided into four sections: Major and Minor Histocompatibility Antigens, Immunobiology of Graft Rejection, Clinical Transplantation, and Frontiers in Transplantation. The first two sections cover present-day understanding of the genetic controls of immunity as well as the two basic concerns of transplantation immunology, namely donor tissue antigens and the host cellular response. The third section deals with clinical aspects of transplantation, while the fourth looks toward future efforts of scientific research in this field—including advances in tolerance and xenotransplantation. A detailed appendix entitled "Molecular Biology for the Clinician" is included to help make the material accessible to readers of all backgrounds. Authored by a wide range of experts in both clinical and research fields, individual chapters cover such topics as: T cell immunity Antigen presentation Alloreactivity Pancreas and islet cell transplantation Allogeneic bone marrow transplantation Models of tolerance induction Xenotransplantation The swine leukocyte antigen (SLA) complex Transplantation Immunology is an ideal teaching text for the fundamental concepts, latest findings, and future directions in this increasingly important field. This volume will appeal to a wide range of clinicians including surgeons and primary-care physicians, as well as scientists in molecular biology and immunology.
Author: Kazuwa Nakao
Publisher: Springer
ISBN: 4431556516
Category : Science
Languages : en
Pages : 330
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Book Description
This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
Author: Richard T. Smith
Publisher: Elsevier
ISBN: 0323146260
Category : Nature
Languages : en
Pages : 553
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Book Description
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.
Author: Brian A. Baldo
Publisher: Springer
ISBN: 3319304720
Category : Medical
Languages : en
Pages : 623
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Book Description
This long overdue title provides a comprehensive, up-to-date, state-of-the art review of approved biologic therapies, with coverage of mechanisms of action, Indications for therapy, immunogenicity and a detailed examination of adverse effects and safety of the many and diverse therapeutic agents presented in a total of 13 chapters. It is predicted that by 2016, biologics will make up half of the world's 20 top-selling drugs and by 2018, biologic medicine sales will account for almost half of the world's 100 biggest selling drugs. Recombinant proteins dominate the growing list of the more than 200 approved biotherapeutic agents with targeted antibodies, fusion proteins and receptors; cytokines; hormones; enzymes; proteins involved in blood-clotting, homeostasis and thrombosis; vaccines; botulinum neurotoxins; and, more recently, biosimilar preparations, comprising the majority of approved biologics. Written with clinicians, other health care professionals, and researchers in mind, Safety of Biologics Therapy examines, in a single volume, the full range of issues surrounding the safety of approved biologic therapies. A good understanding of the risks and safety issues of modern biologics therapy is increasingly being demanded of all those connected with their development, handling, prescribing, administration and subsequent patient management. In addition to being of great value to clinicians in all branches of medicine, and to nurses, pharmacists and researchers, this book will prove invaluable for students taking undergraduate and graduate courses in the above disciplines and in the biomedical sciences.
Author: Nima Rezaei
Publisher: Academic Press
ISBN: 0128140402
Category : Science
Languages : en
Pages : 200
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Book Description
Therapeutic cancer vaccines represent a type of active cancer immunotherapy. Clinicians, scientists, and researchers working on cancer treatment require evidence-based and up-to-date resources relating to therapeutic cancer vaccines. Vaccines for Cancer Immunotherapy provides a reference for cancer treatment for clinicians and presents a well-organized resource for determining high-potential research areas. The book considers that this promising modality can be made more feasible as a treatment for cancer. Chapters cover cancer immunology, general approaches to cancer immunotherapy, vaccines, tumor antigens, the strategy of allogeneic and autologous cancer vaccines, personalized vaccines, whole-tumor antigen vaccines, protein and peptide vaccines, dendritic cell vaccines, genetic vaccines, candidate cancers for vaccination, obstacles to developing therapeutic cancer vaccines, combination therapy, future perspectives and concluding remarks on therapeutic cancer vaccines. - Introduces the feasible immunotherapeutic vaccines for patients with different types of cancer - Presents the status of past and current vaccines for cancer treatment - Considers advantages and disadvantages of different therapeutic cancer vaccines - Looks at the combination of vaccines and other modalities, including immunotherapeutic and conventional methods - Analyzes obstacles to development of therapeutic cancer vaccines - Gives a view on future perspectives in the application of therapeutic cancer vaccines
Author: Per-Ulf Tunn
Publisher: Springer Science & Business Media
ISBN: 3540779604
Category : Medical
Languages : en
Pages : 372
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Book Description
Bone and soft tissue sarcomas represent only about 2% of all malignancies; however, their treatment – with the goal of curing the patient while preserving the functionality of the affected body part – can, unlike other malignancies, only be successful with therapy concepts devised by interdisciplinary teams. This volume provides an extensive up-to-date overview of the specific diagnostics and current treatment standards of these rare entities, presenting the various limb-sparing modalities for patients with bone and soft tissue sarcomas with special regard to innovative reconstructive options. The evaluation of quality of life based on validated scores and the individual methods of coping with the illness through creative artistic projects are also acknowledged and integrated in the whole concept.
