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Chimeric Antigen Receptor T Cell Therapies For Cancer

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Chimeric Antigen Receptor T Cell Therapies for Cancer E Book

Chimeric Antigen Receptor T Cell Therapies for Cancer E Book Book
Author : Daniel W. Lee,Nirali N. Shah
Publisher : Elsevier Health Sciences
Release : 2019-11-30
ISBN : 0323755976
Language : En, Es, Fr & De

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Book Description :

From patient referral to post-therapy management, Chimeric Antigen Receptor (CAR) T-Cell Therapies for Cancer: A Practical Guide presents a comprehensive view of CAR modified T-cells in a concise and practical format. Providing authoritative guidance on the implementation and management of CAR T-cell therapy from Drs. Daniel W. Lee and Nirali N. Shah, this clinical resource keeps you up to date on the latest developments in this rapidly evolving area. Covers all clinical aspects, including patient referral, toxicities management, comorbidities, bridging therapy, post-CAR monitoring, and multidisciplinary approaches to supportive care. Includes key topics on associated toxicities such as predictive biomarkers, infections, and multidisciplinary approaches to supportive care. Presents current knowledge on FDA approved CAR T-cell products as well as developments on the horizon. Editors and authors represent leading investigators in academia and worldwide pioneers of CAR therapy.

Chimeric Antigen Receptor T Cell Therapies for Cancer

Chimeric Antigen Receptor T Cell Therapies for Cancer Book
Author : Daniel W. Lee,Nirali N. Shah, M.D.
Publisher : Elsevier
Release : 2019-12-02
ISBN : 9780323661812
Language : En, Es, Fr & De

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Book Description :

From patient referral to post-therapy management, Chimeric Antigen Receptor (CAR) T-Cell Therapies for Cancer: A Practical Guide presents a comprehensive view of CAR modified T-cells in a concise and practical format. Providing authoritative guidance on the implementation and management of CAR T-cell therapy from Drs. Daniel W. Lee and Nirali N. Shah, this clinical resource keeps you up to date on the latest developments in this rapidly evolving area. Covers all clinical aspects, including patient referral, toxicities management, comorbidities, bridging therapy, post-CAR monitoring, and multidisciplinary approaches to supportive care. Includes key topics on associated toxicities such as predictive biomarkers, infections, and multidisciplinary approaches to supportive care. Presents current knowledge on FDA approved CAR T-cell products as well as developments on the horizon. Editors and authors represent leading investigators in academia and worldwide pioneers of CAR therapy.

Cellular Therapies in Cancer

Cellular Therapies in Cancer Book
Author : Katy Rezvani,Rohtesh S. Mehta
Publisher : Frontiers Media SA
Release : 2020-01-16
ISBN : 2889633780
Language : En, Es, Fr & De

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Book Description :

Download Cellular Therapies in Cancer book written by Katy Rezvani,Rohtesh S. Mehta, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Fast Facts CAR T Cell Therapy

Fast Facts  CAR T Cell Therapy Book
Author : R.J. Buka,A.J. Kansagra
Publisher : Karger Medical and Scientific Publishers
Release : 2021-01-26
ISBN : 3318067423
Language : En, Es, Fr & De

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Book Description :

Chimeric antigen receptor (CAR) T cells are genetically engineered immune cells that can seek out and destroy cancer cells. The results from their use in cancer immunotherapy have been very promising, but treatment is often associated with frequent, serious short-term toxicities. 'Fast Facts: CAR-T Therapy' explains what CAR T cells are and how they were developed, discusses the results of clinical trials and the management of toxicities, and outlines future improvements and applications. It is ideal reading for any healthcare professional wanting to know more about this exciting therapeutic field. Table of Contents: • CAR T cells • Clinical application • Practical aspects • Future directions

CAR T Cell Therapies for Non Hematopoietic Malignancies Taking Off The Training Wheels

CAR T Cell Therapies for Non Hematopoietic Malignancies  Taking Off The Training Wheels Book
Author : Avery Dexter Posey, Jr.,John - Maher,Marcela V. Maus
Publisher : Frontiers Media SA
Release : 2020-04-24
ISBN : 2889636879
Language : En, Es, Fr & De

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Book Description :

Chimeric antigen receptor (CAR) T cell therapies for leukemia (e.g. tisagenlecleucel) and lymphoma (e.g. axicabtagene ciloleucel) have recently received regulatory approval in the United States. Phase I/II trials have demonstrated complete remission of refractory or relapsed tumors in 50% - 94% patients. However, the clinical successes of engineered T cells for the treatment of solid malignancies have thus far been few and far between. Furthermore, several instances of severe and lethal toxicities have arisen due to on-target, off-tumor recognition of antigen by T cell products. Recent advances in phase I trials for solid tumors, as well as in pre-clinical models, have revealed several variables that will be important to consider for the successful use of CAR-T cells in treating solid tumors. These variables include (i) regional versus systemic delivery; (ii) scFv versus ligand interactions; (iii) antigen loss versus escape; (iv) epitope spreading and (v) checkpoint expression on immune cells or tumor cells. Also, there remains outstanding mechanistic questions related to why differences exist in the persistence and tonic signaling of second-generation CD28 versus 4-1BB co-stimulated CAR-T cells. In addition, we are now learning the roles of lympho-depleting regimens (and associated toxicities) in modifying the persistence of engineered T cell therapies. A more comprehensive view of CAR-T cell strategies and important advances, both of pre-clinical and clinical evaluations, in solid tumors is necessary to drive these therapies forward.

Development of Biomaterials for Chimeric Antigen Receptor CAR T Cell Therapy

Development of Biomaterials for Chimeric Antigen Receptor  CAR  T Cell Therapy Book
Author : Brynn Riann Olden
Publisher : Unknown
Release : 2018
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Chimeric antigen receptor (CAR) T cell therapy has emerged as an effective new cancer treatment that genetically reprograms a patient’s T cells to recognize an epitope specifically expressed on the surface of cancer cells and trigger cytotoxic action against those cancer cells. This therapy has been especially effective in the treatment of CD19+ hematologic malignancies. However, the manufacturing of these autologous cell therapies requires laborious processing steps that present multiple challenges and opportunities for innovation, described in Chapter 1. The current manufacturing system requires extensive use of biologic reagents including antibody-coated magnetic beads for manipulation and expansion, and retroviruses for genetic modification of ex vivo cultured T cells. In this work, three classes of synthetic biomaterials are developed to improve and study the ex vivo expansion and genetic modification of primary human T cells. In Chapter 2, we describe the development of cell-templated supported lipid bilayers as a platform for studying the effect of activation particle design on polyclonal T cell expansion and differentiation. Chapter 3 describes work towards identifying synthetic peptide and aptamer targeting ligands for T cell activation through library screening techniques. In Chapters 4 and 5, we report the use of cationic polymers of defined architecture for non-viral gene delivery to T cells and study the underlying barriers to improved gene delivery in T cells. The major findings from this work are summarized in Chapter 6 where we also make recommendations for future applications and directions of this work.

Chimeric Antigen Receptor T Cell Therapy for the Community Oncologist

Chimeric Antigen Receptor T   Cell Therapy for the Community Oncologist Book
Author : Anonim
Publisher : Unknown
Release : 2016
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Abstract : The field of cancer immunotherapy has rapidly progressed in the past decade as several therapeutic modalities have entered into the clinic. One such immunotherapy that has shown promise in the treatment of cancer is the use of chimeric antigen receptor (CAR)‐modified T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T‐cell signaling and costimulatory domains that can be used to reprogram a patient's T cells to specifically target tumor cells. CAR T‐cell therapy has demonstrated sustained complete responses for some patients with advanced leukemia, and a number of CAR therapies are being evaluated in clinical studies. CAR T‐cell therapy‐associated toxicities, including cytokine release syndrome, macrophage activation syndrome, and tumor lysis syndrome, have been observed and effectively managed in the clinic. In patients with significant clinical responses, sustained B‐cell aplasia has also been observed and is a marker of CAR T‐cell persistence that might provide long‐term disease control. Education on CAR T‐cell therapy efficacy and safety management is critical for clinicians and patients who are considering this novel type of treatment. In the present report, the current landscape of CAR T‐cell therapy, the effective management of patients undergoing treatment, and which patients are the most suitable candidates for current trials are discussed. Implications for Practice: The present report describes the current status of chimeric antigen receptor (CAR) T lymphocytes as an immunotherapy for patients with relapsed or refractory B‐cell malignancies. CAR T cells targeting CD19, a protein expressed on many B‐cell malignancies, typically induce high complete response rates in patients with B‐cell leukemia or lymphoma who have very limited therapeutic options. Recent clinical trial results of CD19 CAR T‐cell therapies and the management of CAR T‐cell‐associated adverse events are discussed. The present report will therefore inform physicians regarding the efficacy and safety of CAR T cells as a therapy for B‐cell malignancies. Abstract : An immunotherapy that has shown promise in cancer treatment is chimeric antigen receptor‐modified (CAR‐modified) T lymphocytes. CARs are engineered receptors constructed from antigen recognition regions of antibodies fused to T‐cell signaling and costimulatory domains that reprogram a patient's T cells to specifically target tumor cells. The current landscape of CAR T‐cell therapy, effective management of patients undergoing treatment, and the most suitable candidates for current trials are discussed.

Tumor Immunology and Immunotherapy

Tumor Immunology and Immunotherapy Book
Author : Robert C. Rees
Publisher : Oxford University Press, USA
Release : 2014-05-20
ISBN : 0199676860
Language : En, Es, Fr & De

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Book Description :

Patients are beginning to benefit from antibody based, cellular and vaccine approaches that are effective against genetically diverse and therapy-resistance cancers. BCG immunotherapy is now being used as a first line treatment for human bladder cancer and the introduction of prophylactic vaccination against Hepatitis B and HPV cancers is starting to show positive results. Following recent FDA approval for a vaccination against prostate cancer, and optimistic results in clinical trials for a vaccine targeting cancer antigens in lung cancer, cancer immunotherapy is now significantly impacting patient clinical management. Tumor Immunology and Immunotherapy provides an up-to-date and comprehensive account of cancer immunity and immunotherapy. It discusses our adaptive and innate immunity to cancer, the mechanisms underpinning our immune response, current approaches to cancer immunotherapy, and how tumour and host responses can circumvent effective anti-cancer immunity. The book examines recent results, publications and current areas of interest including 'immune editing' and the specific issues that are affecting the research and development of vaccines, providing insight into how these problems may be overcome, as viewed by world leaders in the field. Tumor Immunology and Immunotherapy will appeal to clinicians working in oncology and cancer immunotherapy, and research scientists including PhD and masters students, post-doctoral researchers and senior investigators.

The Development of Novel T Cell Receptor and Chimeric Antigen Receptor Engineered T Cell Therapies for the Treatment of Cancer

The Development of Novel T Cell Receptor  and Chimeric Antigen Receptor  Engineered T Cell Therapies for the Treatment of Cancer Book
Author : Vanessa Tubb
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download The Development of Novel T Cell Receptor and Chimeric Antigen Receptor Engineered T Cell Therapies for the Treatment of Cancer book written by Vanessa Tubb, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Investigating the Efficacy of CAR T Cells Expressing TQM 13 in Targeting Glioblastoma

Investigating the Efficacy of CAR T Cells Expressing TQM 13 in Targeting Glioblastoma Book
Author : Hali A Jiang
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Chimeric antigen receptor (CAR) modified T-cell therapy has proven to be an attractive immunotherapy that involves the genetic modification of T-lymphocytes to target specific antigens expressed by cancer cells. Recent research has shown promising results for CAR T-cells expressing Targeted Quadruple Mutant-13 (TQM-13), a mutant version of interleukin-13 (IL-13), in targeting and attacking glioblastoma multiforme (GBM). CAR T immunotherapy is able to utilize the inherent ability of T-lymphocyte cells to migrate across the blood-brain barrier (BBB), a specialized, highly selective, semipermeable membrane formed by neurovascular endothelial cells that restrict the substances that enter and exit the central nervous system. Additionally, the CAR modification leads to specialized targeting of a specific antigen displayed by the tumor of interest. Once attached and bound to the target, the CAR T-cell becomes activated leading to T-cell proliferation, secretion of apoptosis-inducing proteins, and subsequent destruction of the tumor cells. The present study examines the ability of CAR T-cells expressing TQM-13 to target GBM. The results indicate that CAR modification did not impede the cells natural ability to form intercellular gaps nor their ability to extravasate through an endothelial layer, both crucial steps in crossing the BBB. Additionally, it was found that CAR modification significantly increased both the total number of adhesions observed as well as the length of time the CAR T-cells adhered to GBM cells under flow conditions. These results imply that a TQM-13 directed CAR design has the potential to be a powerful therapeutic tool in the treatment of GBM.

Developments in T Cell Based Cancer Immunotherapies

Developments in T Cell Based Cancer Immunotherapies Book
Author : Paolo A. Ascierto,David F. Stroncek,Ena Wang
Publisher : Humana Press
Release : 2015-11-26
ISBN : 3319211676
Language : En, Es, Fr & De

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Book Description :

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.

Engineering Bispecific Chimeric Antigen Receptors to Improve the Efficacy of Adoptive T cell Therapy

Engineering Bispecific Chimeric Antigen Receptors to Improve the Efficacy of Adoptive T cell Therapy Book
Author : Eugenia Zah
Publisher : Unknown
Release : 2018
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The recent FDA approval of CD19 chimeric antigen receptor (CAR) adoptive T-cell therapy for B-cell leukemias serves to highlight CAR-T cell therapy as a promising treatment approach for refractory cancers. More recently, adoptive transfer of T cells expressing CARs targeting B-cell maturation antigen (BCMA) has had numerous successes in clinical trial with 80-100% of multiple myeloma patients responding to treatment. However, CAR-T-cell therapy still faces several limitations including tumor antigen escape, a circumstance where tumor cells downregulate their surface antigen to avoid detection by CAR-T cells, and T-cell inhibition by cytokines such as transforming growth factor (TGF)- in the solid tumor environment. These factors can significantly limit the efficacy of CAR-T-cell therapy. To overcome antigen escape, we designed single-chain bispecific CARs (OR-gate CARs) capable of signaling in the presence of two antigens instead of one. Using rational design principles, we constructed and evaluated CD19-OR-CD20 CARs that are able to prevent tumor antigen escape by CD19- leukemia. We further demonstrate that unlike single-input CD19 CARs, CD19-OR-CD20 CARs also prevent the emergence of spontaneous CD19-downregulated tumors in vivo. In a second study, we describe the rapid design and characterization of BCMA-OR-CS1 CARs and demonstrate that BCMA-OR-CS1 CARs can be rationally engineered to prevent antigen escape by BCMA- as well as CS1- myeloma cells. Finally, we explore the utility of the TGF- CAR, a receptor capable of rewiring inhibitory TGF- signaling to an activating response, in improving CD20 CAR function in TGF- -rich environments. We evaluated three different bispecific targeting strategies, OR-gate CAR, DualCAR (co-expressing two receptors in one cells), and CARpool (pooling two different CAR-T cells), and demonstrate that TGF- CAR-T cells are able to shield neighboring CD20 CAR-T cells from the inhibitory effects of TGF- .

Engineering and Evaluating Chimeric Antigen Receptor T Cell Potency Ex Vivo and in Vitro

Engineering and Evaluating Chimeric Antigen Receptor T Cell Potency Ex Vivo and in Vitro Book
Author : Nicole J. Piscopo
Publisher : Unknown
Release : 2020
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Chimeric antigen receptor (CAR) T cells are genetically engineered T cells that have been used to target cancer-associated antigens [1]. The profound success of CAR T cells in treating hematological malignancies (e.g. leukemia by targeting CD19) has led to the FDA approval of three CAR T cell products [2]. CAR T cells are primarily engineered via viral methods which insert the CAR transgene into random locations in the genome resulting in varied expression and signal activation of the CAR [3]. As a result, CAR T cell performance can vary greatly from cell to cell even within the same batch, due in part to the heterogeneity of CAR activity within the gene-modified T cell population [4]. Therefore, to better ensure that manufactured CAR T cells will result in cancer remission, improvements to the manufacturing process must be made to certify that the live cellular products will act accordingly once they are delivered to the patient [5]. This thesis aims to engineer precise control over the location of integration and copy number afforded by CRISPR-Cas9 gene editing tools to create more homogenous expression of the CAR in the manufactured CAR T cell population, resulting in less variance in potency of individual CAR T cells. First, I describe the manufacture and measurement of expression and function within virally generated and CRISPR-Cas9 generated CAR T cell products. Next, I detail the in vitro functional analysis of CAR T cells within microwell co-cultures with target cancer cells to allow for measure of in vitro activity of the CAR+ cells and acquire relevant parameters for mathematical models. Finally, I share the results of in vivo testing and computational modeling of CAR T cell therapies within murine xenograft models. This work demonstrates the value of precise gene editing in CAR T cell manufacture, and its influence on quality assurance and quality control (QA/QC) methods of CAR T cell products.

Designing Chimeric Antigen Receptors to Effectively and Safely Target Tumors

Designing Chimeric Antigen Receptors to Effectively and Safely Target Tumors Book
Author : Anonim
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Highlights: Description of structural elements of chimeric antigen receptors used to engineer T cells. Differences between T cell receptor and chimeric antigen receptor recognition. Types of T cells that can be engineered to target tumor cells. Strategies for augmenting function and selectivity of chimeric antigen receptors. Strategies for improving safety of chimeric antigen receptor modified T cells. Abstract : The adoptive transfer of T cells engineered to express artificial chimeric antigen receptors CARs) that target a tumor cell surface molecule has emerged as an exciting new approach for cancer immunotherapy. Clinical trials in patients with advanced B cell malignancies treated with CD19-specific CAR-modified T cells (CAR-T) have shown impressive antitumor efficacy, leading to optimism that this approach will be useful for treating common solid tumors. Because CAR-T cells recognize tumor cells independent of their expression of human leukocyte antigen (HLA) molecules, tumors that escape conventional T cells by downregulating HLA and/or mutating components of the antigen processing machinery can be eliminated. The ability to introduce or delete additional genes in T cells has the potential to provide therapeutic cell products with novel attributes that overcome impediments to immune mediated tumor elimination in immunosuppressive tumor microenvironments. This review will discuss recent concepts in the development of effective and safe synthetic CARs for adoptive T cell therapy (ACT).

Basics of Chimeric Antigen Receptor CAR Immunotherapy

Basics of Chimeric Antigen Receptor  CAR  Immunotherapy Book
Author : Mumtaz Y. Balkhi
Publisher : Academic Press
Release : 2019-07-31
ISBN : 0128197471
Language : En, Es, Fr & De

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Book Description :

Basics of Chimeric Antigen Receptor (CAR) Immunotherapy presents the latest on how T cell adoptive immunotherapy has progressed in its ultimate goal of curing metastatic malignant cancers. Recent clinical data obtained with checkpoint receptor blockade inhibitors and chimeric antigen receptor (CAR) therapy has been especially promising, thus generating renewed hope that we may be on the verge of finally curing cancer. Over the years, huge progress has been made in controlling several stage IV metastasized cancers through the clinical application of checkpoint receptor inhibitory drugs and CAR-Therapy that has seen unprecedented interest in the immunotherapy field. Presents the first book to provide a basic understanding of chimeric antigen receptor (CARs) design, production and clinical application protocols Provides unique authority as the editor has worked directly with CARs Discusses the challenges encountered in actual clinical trials and how these challenges can be overcome Includes a full chapter on various challenges researchers should expect to encounter in the CAR-therapy field

Cell and Gene Therapies

Cell and Gene Therapies Book
Author : Miguel-Angel Perales,Syed A. Abutalib,Catherine Bollard
Publisher : Springer
Release : 2018-11-27
ISBN : 3319543687
Language : En, Es, Fr & De

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Book Description :

In this book, experts in the field express their well-reasoned opinions on a range of complex, clinically relevant issues across the full spectrum of cell and gene therapies with the aim of providing trainee and practicing hematologists, including hematopoietic transplant physicians, with information that is relevant to clinical practice and ongoing research. Each chapter focuses on a particular topic, and the concise text is supported by numerous working tables, algorithms, and figures. Whenever appropriate, guidance is provided regarding the availability of potentially high-impact clinical trials. The rapid evolution of cell and gene therapies is giving rise to numerous controversies that need to be carefully addressed. In meeting this challenge, this book will appeal to all residents, fellows, and faculty members responsible for the care of hematopoietic cell transplant patients. It will also offer a robust, engaging tool to aid vital activities in the daily work of every hematology and oncology trainee.

Current Immunotherapeutic Strategies in Cancer

Current Immunotherapeutic Strategies in Cancer Book
Author : Matthias Theobald
Publisher : Springer Nature
Release : 2019-08-31
ISBN : 3030237656
Language : En, Es, Fr & De

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Book Description :

This book offers a comprehensive review of recent advances in cancer immunotherapy, and explores the value and limitations of the most effective current therapeutic strategies and emerging treatment modalities. It discusses in detail the successes achieved using monoclonal antibodies (mAbs), including developments with regard to conjugated mAbs and also bispecific mAbs as novel treatment options for leukemia and solid tumors. It also examines the advances toward personalized immunotherapy, focusing on the effectiveness of adoptive cell therapy using genetically engineered T cells with tumor-associated antigen-specific T-cell receptors and chimeric antigen receptors, as well as the role of tailored vaccines based on the patient’s cancer mutanome. Further, it describes the impressive therapeutic results recently achieved with checkpoint inhibitors, and analyzes novel strategies to modulate the immunosuppressive tumor microenvironment. Written by leading international experts and providing up-to-date information on emerging strategies, such as oncolytic virus-based therapy, epigenetic therapy, and combination therapy, the book appeals to all those with an interest in immunotherapy as it comes of age.

Targeted Therapies in Cancer

Targeted Therapies in Cancer Book
Author : Marc Lacroix
Publisher : Unknown
Release : 2016
ISBN : 9781634846684
Language : En, Es, Fr & De

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Book Description :

Download Targeted Therapies in Cancer book written by Marc Lacroix, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Critical Reviews in Immunology

Critical Reviews in Immunology Book
Author : Anonim
Publisher : Unknown
Release : 2009
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Critical Reviews in Immunology book written by , available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.