Dissecting the Mechanism of T Cell Tolerance for More Effective Breast Cancer Vaccine Development PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Dissecting the Mechanism of T Cell Tolerance for More Effective Breast Cancer Vaccine Development PDF full book. Access full book title Dissecting the Mechanism of T Cell Tolerance for More Effective Breast Cancer Vaccine Development by . Download full books in PDF and EPUB format.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 25
Get Book Here
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
Get Book Here
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 : 0
Get Book Here
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: Laurence Zitvogel
Publisher: Springer
ISBN: 3319624318
Category : Medical
Languages : en
Pages : 700
Get Book Here
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: Kazuwa Nakao
Publisher: Springer
ISBN: 4431556516
Category : Science
Languages : en
Pages : 330
Get Book Here
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: Nima Rezaei
Publisher: Academic Press
ISBN: 0128140402
Category : Science
Languages : en
Pages : 200
Get Book Here
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
Get Book Here
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.
Author: Tim F. Greten
Publisher: Springer
ISBN: 9783319879116
Category : Medical
Languages : en
Pages : 0
Get Book Here
Book Description
In this book we provide insights into liver – cancer and immunology. Experts in the field provide an overview over fundamental immunological questions in liver cancer and tumorimmunology, which form the base for immune based approaches in HCC, which gain increasing interest in the community due to first promising results obtained in early clinical trials. Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death in the United States. Treatment options are limited. Viral hepatitis is one of the major risk factors for HCC, which represents a typical “inflammation-induced” cancer. Immune-based treatment approaches have revolutionized oncology in recent years. Various treatment strategies have received FDA approval including dendritic cell vaccination, for prostate cancer as well as immune checkpoint inhibition targeting the CTLA4 or the PD1/PDL1 axis in melanoma, lung, and kidney cancer. Additionally, cell based therapies (adoptive T cell therapy, CAR T cells and TCR transduced T cells) have demonstrated significant efficacy in patients with B cell malignancies and melanoma. Immune checkpoint inhibitors in particular have generated enormous excitement across the entire field of oncology, providing a significant benefit to a minority of patients.
Author: Aung Naing
Publisher: Springer Nature
ISBN: 3030793087
Category : Medical
Languages : en
Pages : 445
Get Book Here
Book Description
The field of immuno-oncology continues to rapidly evolve as new insights to fight and treat cancer emerge. The fourth edition of Immunotherapy provides the most current overview of immuno-oncology in different cancer types and toxicities associated with immunotherapy. While immunotherapy has revolutionized the treatment landscape of several solid malignancies, several challenges still exist. Only a subset of patients derive clinical benefits; some do not respond at all, and others respond initially, only for their disease to progress later. Because these drugs can activate a broad range of immune cells, patients suffer from a unique set of side effects known as immune-related adverse events. As more immunotherapeutic agents are used in the clinic, it is important to provide updates about current and ongoing developments in the field to further research efforts and inform treatment decisions. The fourth edition will have a new focus on strategies to overcome the challenges associated with immunotherapy. Chapters will discuss topics such as biomarkers of response, resistance mechanisms, role of imaging in predicting immune-related adverse events, and management of immune-related adverse events. Written by leading experts conducting cutting-edge research, readers will gain up-to-date knowledge on the current state and future of immunotherapy.
Author: Alexander von Gabain
Publisher: Springer Science & Business Media
ISBN: 3709107091
Category : Medical
Languages : en
Pages : 318
Get Book Here
Book Description
“Development of novel vaccines” gives an overview of the tasks in basic research leading to the final product – the vaccine and its applications, belonging to the most complex biologics in the pharmaceutical field. Distinct from most textbooks in the vaccine arena, the current issue focuses on the translational aspect, namely, how research results can be transformed into life-saving medical interventions. Each chapter of the book deals with one important paradigm for the development of novel vaccines, along the value chain towards the final vaccine, and furthermore, with the inevitable tools required for this process. Contributions are prepared by teams of scientists, all of whom are experts in the field, most of them anchored in biomedical organizations devoted to translational culture, thereby lighting the certain topics from different views. This volume is a must read for researchers engaged in vaccine development and who really want to see their research results to become a product.
Author: Douglas B. Lowrie
Publisher: Springer Science & Business Media
ISBN: 1592596886
Category : Medical
Languages : en
Pages : 530
Get Book Here
Book Description
The field of DNA vaccines has undergone explosive growth in the last few years. As usual, some historical precursors of this approach can be d- cerned in the scientific literature of the last decades. However, the present state of affairs appears to date from observations made discreetly in 1988 by Wolff, Malone, Felgner, and colleagues, which were described in a 1989 patent and published in 1990. Quite surprisingly, they showed that genes carried by pure plasmid DNA and injected in a saline solution, hence the epithet “naked DNA,” could be taken up and expressed by skeletal muscle cells with a low but reproducible frequency. Such a simple methodology was sure to spawn many applications. In a separate and important line of experimentation, Tang, De Vit, and Johnston announced in 1992 that it was indeed possible to obtain humoral immune responses against proteins encoded by DNA delivered to the skin by a biolistic device, which has colloquially become known as the “gene gun. ” The year 1993 saw the publication of further improvements in the me- ods of naked DNA delivery and, above all, the first demonstrations by several groups of the induction of humoral and cytotoxic immune responses to viral antigens expressed from injected plasmid DNA. In some cases, protection against challenge with the pathogen was obtained. The latter result was - questionably the touchstone of a method of vaccination worthy of the name.
