Ex Vivo Manipulation Of Cd8 T Cells To Improve Adoptive Cell Therapy Against Cancer
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Ex Vivo Manipulation Of Cd8 T Cells To Improve Adoptive Cell Therapy Against Cancer
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Author : Henry Leonard
language : en
Publisher:
Release Date : 2018
Ex Vivo Manipulation Of Cd8 T Cells To Improve Adoptive Cell Therapy Against Cancer written by Henry Leonard and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Ex Vivo Manipulation Of Cd8 T Cells To Improve Adoptive Cell Therapy Agaisnt Cancer
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Author : Henry Leonard
language : en
Publisher:
Release Date : 2018
Ex Vivo Manipulation Of Cd8 T Cells To Improve Adoptive Cell Therapy Agaisnt Cancer written by Henry Leonard and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018 with categories.
Developments In T Cell Based Cancer Immunotherapies
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Author : Paolo A. Ascierto
language : en
Publisher: Humana
Release Date : 2019-03-14
Developments In T Cell Based Cancer Immunotherapies written by Paolo A. Ascierto and has been published by Humana this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-03-14 with Medical categories.
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.
Generating Memory T Cell Responses To Cancer
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Author : Jacob Stuart Bowers
language : en
Publisher:
Release Date : 2017
Generating Memory T Cell Responses To Cancer written by Jacob Stuart Bowers and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
The development of immunotherapies over the last three decades has dramatically improved treatment for late stage cancers. Among these therapies is adoptive T cell therapy (ACT), which enriches and expands autologous tumor-reactive T cells for reinfusion to the patient. ACT has exploited the power of T cells to exert long-term immunity providing unprecedented responses, including complete remissions and cures. Three major benefits of ACT have emerged since the early trails: 1) ACT provides a window for preconditioning the patient. This allows transferred T cells to engraft in large numbers, become functionally enhanced, and be free of immunosuppressive pressure. 2), ACT allows for the selection of T cells with superior antitumor qualities for treatment. 3), The ex vivo expansion period allows for further manipulation of those T cells to enhance their antitumor capacity. Also, an overarching theme in ACT is that complete and durable responses are possible in patients who recieve T cells capable of longterm memory responses. We examined the impact of each element of the ACT regimen on the memory of T cells including how preconditioning influences memory and function, thae advantage of employing IL-17 producing CD4+ T cells (TH17) cells with durable memory properties, and how to endow CD8+ T cells improve memory capacity through blackade of the P13Ko pathway. We discovered we can ex vivo prime T cells with IL-12 to mimic the potentiating effect of an activated innate immune system to improve the longevity of antitumor immunity and reduce the dose of total body irradiation (TBI). We also report that Th17 cells naturally express stem memory, which allows for expansion to high numbers of durable effectors and long-lasting immunity against tumors. FInally, peripheral T cells genetically redirected against tumors with chimeric antigen receptors (CAR T cells) can be enahanced by pharmaceutical blockade of PI3Ko endowing a durable memory phenotype that controls tumor after conventional CAR T cells fail. Thus, this dissertation provides evidence that at each step in the ACT protocol, T cells can be selected, or enhanced to exert powerful memory immunity that translates into durable responses in patients with late stage malignancies.
Negative Co Signaling In The Expansion And Function Of Human Antigen Specific T Cells For Adoptive Cell Therapy
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Author : Shirin Lak
language : en
Publisher:
Release Date : 2021
Negative Co Signaling In The Expansion And Function Of Human Antigen Specific T Cells For Adoptive Cell Therapy written by Shirin Lak and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
Immunotherapy, especially the adoptive transfer of T cells and immune checkpoint blockade therapy, have revolutionized cancer therapy. In particular, utilizing antigen-specific T cells for adoptive cell therapy has enabled the development of specific and effective strategies. It has paved the way for developing more accurate and personalized cancer immunotherapies. Adoptive cell therapy (ACT) results depend on the characteristics of ex vivo expanded T cells, such as their differentiation and clonal diversity. However, ex vivo expanded specific T cells often express several inhibitory receptors involved in T-cell exhaustion and markers of terminal effector differentiation. Accordingly, we hypothesized that blocking one or several inhibitory receptors during the ex vivo expansion could improve the expansion and differentiation of antigen-specific T cells. Preconditioning the ACT products and combinatorial immunotherapy approaches are newly developed concepts in cancer therapy to optimize cancer immunotherapy for a larger group of patients. To study the development of antigen-specific T-cells in combination with checkpoint blockade, we have adopted a method that allows the expansion of rare antigen-specific T cell precursors from PBMCs via multiple stimulations, using antigen-pulsed dendritic cells. In the current study, we utilized our protocol to generate and expand antigen-specific CD8+ T cells targeting the oncogenic Epstein-Barr virus (EBV)-LMP2 and a tumor-associated antigen (TAA) from the Wilms Tumor 1 (WT1) protein. We employed two approaches to abolish the negative regulatory receptors, antibody-mediated blockade and deletion via CRISPR/Cas9. We evaluated the impact of checkpoint blockade on antigen-specific T cells development, proliferation, and function. Additionally, TCR clonality and transcriptomic changes were assessed by genomic studies, including single-cell RNA (scRNA) sequencing and T-cell receptor sequencing. Supporting our hypothesis, we observed that blocking both PD-L1 and TIM3 (not any of them alone) significantly enhanced LMP2 and WT1-specific T cell generation and expansion. Additionally, checkpoint blockade resulted in higher specific T cell function, including cytokine production and in vitro targeted cytotoxicity. Using scRNA-seq and TCR sequencing approaches, we first remarked that the specific T cells are highly oligoclonal and identified a few dominant shared clones between donors. Immune checkpoint blockade did not confer consistent transcriptional signatures but may have a clonotype and donor-specific impact on the expression of activation and exhaustion-related genes. Overall, immune checkpoint blockade did not markedly alter the clonal composition of the T-cell product. We also evaluated the impact of CD5 deletion in antigen-specific T cell priming and expansion as an inhibitory receptor and a part of the immune response synapse. However, in a human ACT setting, our data show that the CRISPR/Cas9 mediated CD5 deletion only has modest effects on antigen-specific T-cell generation. However, future combinations with the blockade of other immune checkpoint may be warranted. Conclusion We demonstrated that blocking PD-L1 and TIM3 during the ex vivo expansion improves antigen-specific T-cell yield. We show that blocking multiple checkpoints can synergistically optimize specific T-cell production without compromising the response's specificity. It is a rapidly implementable strategy to enhance the number and quality of ex vivo expanded antigen-specific T cells for immunotherapy.
Epstein Barr Virus Volume 2
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Author : Christian Münz
language : en
Publisher: Springer
Release Date : 2015-10-01
Epstein Barr Virus Volume 2 written by Christian Münz and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-10-01 with Medical categories.
Epstein Barr virus (EBV) was discovered as the first human tumor virus around 50 years ago. Since its discovery in Burkitt’s lymphoma it has been associated with various other malignancies, infectious mononucleosis and even autoimmune diseases. The two book volumes on EBV summarize the first 50 years of research on this tumor virus, starting with historical perspectives on discovery, oncogenicity and immune control, reviewing the role that the virus plays in the various associated diseases and concluding with a discussion on how the immune system keeps persistent EBV infection under control in healthy EBV carriers and can be used to treat EBV associated diseases. The respective 32 chapters are written by international experts from three continents for health care providers, biomedical researchers and patients that are affected by EBV. The assembled knowledge should help to understand EBV associated diseases better and to develop EBV specific vaccination in the near future.
Ex Vivo Cell Therapy
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Author : Klaus Schindhelm
language : en
Publisher: Academic Press
Release Date : 1999
Ex Vivo Cell Therapy written by Klaus Schindhelm and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1999 with Health & Fitness categories.
R.E. Nordon and K. Schindhelm, Introduction. -- L. Robb, A.G. Elefanty, and C.G. Begley, Transcriptional Control of Hematopoieses. -- R. Starr and N.A. Nicola, Cell Signaling by Hemopoietic Growth Factor Receptors. -- P.J. Simmons, D.N. Haylock, and J.-P. Lévesque, Influence of Cytokines and Adhesion Molecules on Hematopoietic Stem Cell Development. -- P.A. Rowlings, Allogeneic Hematopoietic Stem Cell Transplantation. -- U. Hahn and L.B. To, Autologous Stem Cell Transplantation. -- M.R. Vowels, Cord Blood Stem Cell Transplantation. -- S.R. Riddell, E.H. Warren, D. Lewinsohn, C. Yee, and P.D. Greenberg, Reconstitution of Immunity by Adoptive Immunotherapy with T Cells. -- L.Q. Sun, M. Miller, and G. Symonds, Exogenous Gene Transfer into Lymphoid and Hematopoietic Progenitor Cells. -- C. Dowding, T. Leemhuis, A. Jakubowski, and C. Reading, Process Development for Ex Vivo Cell Therapy. -- R.E. Nordon and K. Schindhelm, Cell Separation. -- P.W. Zandstra, C.J. Eaves, and J.M. Piret, Environ ...
Brain Tumor Immunotherapy
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Author : Linda M. Liau
language : en
Publisher: Springer Science & Business Media
Release Date : 2000-11-10
Brain Tumor Immunotherapy written by Linda M. Liau and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000-11-10 with Medical categories.
An authoritative panel of researchers and clinicians critically reviews the entire field to provide a comprehensive guide to modern brain tumor immunotherapy and thereby enhance future research in this area. The contributors detail many of the key laboratory experiments and clinical protocols that are currently being investigated, integrate the available information from previous and ongoing research, and help define the current status of the field. Topics range from adoptive cellular and antibody-mediated immunotherapy of brain tumors to tumor vaccines and related strategies, and include many vanguard experimental strategies and immunological techniques for studying brain tumor immunotherapy. Cutting-edge and comprehensive, Brain Tumor Immunotherapy brings together all the important recent advances in our understanding of central nervous system tumor immunology and illustrates in powerful detail the many new applications now harnessing the immune response for brain tumor therapeutics.
Guide To Immunotherapy
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Author : Suzanne L. Walker
language : en
Publisher:
Release Date : 2018-10
Guide To Immunotherapy written by Suzanne L. Walker and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-10 with categories.
Adoptive Immunotherapy
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Author : Burkhard Ludewig
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-02-02
Adoptive Immunotherapy written by Burkhard Ludewig and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-02-02 with Medical categories.
An authoritative collection of optimal techniques for producing and characterizing the immunologically active cells and effector molecules now gaining wide use in the clinical treatment of patients. Taking advantage of the latest technologies, the authors present readily reproducible experimental protocols for the study of dendritic cells, T cells, monoclonal antibodies, and bone marrow transplantation. The emphasis is on preclinicical and clinical applications and on the progress of selected approaches in clinical trials. Additional chapters cover the molecular definition of target antigens, mathematical modeling approaches to immunotherapy, and the utilization of regulatory T cells. The protocols make it possible to study the adoptive transfer of tailored antigen-specific immune cells and to improve the clinical application of adoptive immunotherapy.