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Basics Of Chimeric Antigen Receptor Car Immunotherapy

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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

Part I Understanding Cancer Immunotherapy A brief Review Part II What is Chimeric Antigen Receptor CAR T Cell Therapy An Emerging Cancer Treatment Modality

Part I  Understanding Cancer Immunotherapy  A brief Review  Part II     What is Chimeric Antigen Receptor  CAR  T  Cell Therapy     An Emerging Cancer Treatment Modality  Book
Author : Dr. Hakim Saboowala
Publisher : Dr.Hakim Saboowala
Release : 2020-05-12
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Part I- Understanding Cancer Immunotherapy: A brief Review. Immunotherapy, also called biologic therapy, is a type of cancer treatment that boosts the body's natural defenses to fight cancer. It uses substances made by the body or in a laboratory to improve or restore immune system function. Immunotherapy may work by: Stopping or slowing the growth of cancer cells Stopping cancer from spreading to other parts of the body Helping the immune system work better at destroying cancer cells There are several types of immunotherapy, including: Monoclonal antibodies and tumor-agnostic therapies Non-specific immunotherapies Oncolytic virus therapy T-cell therapy Cancer vaccines Part II- “What is Chimeric Antigen Receptor (CAR) T- Cell Therapy?” An Emerging Cancer Treatment Modality. Chimeric antigen receptor (CAR) T-cell therapy is an emerging cancer treatment modality in which the patients’ own immune cells are collected, genetically engineered to recognize a tumor-related target, expanded in vitro, and then reinfused to produce responses and prevent progression in a variety of malignancies (ie, adoptive cell transfer) Several types of adoptive cell transfer(ACT) are under investigation, but CAR T-cell therapy is the first to enter clinical practice. Like other technologies, CAR-T cell therapy has undergone a long development process in the past. Chimeric antigen receptor- (CAR-) T cell therapy is one of the most recent innovative immunotherapies and is rapidly evolving. At present, CAR-T cell therapy is developing rapidly, and many clinical trials have been established on a global scale, which has great commercial potential. I have endeavored to compile this E- Booklet into Two Parts i.e. Part I & Part II for better understanding of Chimeric antigen receptor (CAR) T-cell therapy, an emerging cancer treatment modality. In Part I, an effort has been made to describe Cancer Immunotherapy briefly whereas in Part II know about of CAR T-Cell Therapy-the first to enter clinical practice- has been embodied. Further it is attempted to describe toxicity of CAR-T cell therapy briefly and future development and opportunities for immunotherapy. …Dr. H. K. Saboowala. M.B.(Bom) .M.R.S.H.(London)

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.

Defining Optimal T Cell Characteristics for Pediatric Chimeric Antigen Receptor CAR T Cell Trials

Defining Optimal T Cell Characteristics for Pediatric Chimeric Antigen Receptor  CAR  T Cell Trials Book
Author : Julie M. Rivers
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Background: Engineered chimeric antigen receptor (CAR) T cells have emerged as a powerful, highly personalized immunotherapy in pediatric cancer. Early phase clinical trials using CAR T cells targeting CD19 have resulted in complete response (CR) rates as high as 93% in children with relapsed and refractory acute lymphoblastic leukemia (ALL). Despite this success, there are many challenges that must be overcome before CAR T cell therapy can be used routinely in pediatric ALL or other malignancies. Objective: To develop novel biomarkers that will identify patients at high risk for poor product expansion, treatment failure and/or toxicity with current immunotherapy protocols and that may ultimately help improve manufacturing methods to produce safer and more effective CAR T cells. Design/Methods: Using flow cytometry, we evaluated T cell characteristics (memory phenotype, cytokine production, presence of markers of activation/exhaustion) of starting products in 43 patients enrolled and treated in a Phase I clinical trial, PLAT-02. Potential predictors of poor product expansion were assessed using the Wilcoxon Rank Sum Test. Results: A higher percentage of cells producing cytokines and expressing PD-1 in CD4 starting products was associated with poor expansion. Poor expansion was not associated with patient toxicities or outcomes. Discussion: Increased cytokine production and PD-1 expression suggest a more differentiated, effector-like phenotype of starting products that subsequently experience poor expansion, consistent with preclinical data, although numbers are limited. Conclusion: Ongoing correlative biology studies will be important in future immunotherapy trials as we seek to identify biomarkers that predict product expansion, toxicities and outcomes.

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.

Immunotherapy Using Chimeric Antigen Receptor Macrophage

Immunotherapy Using Chimeric Antigen Receptor Macrophage Book
Author : Peng Fei Huang
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Chimeric antigen receptor (CAR) T cell immunotherapy has become one of the most prominent and leading cancer therapies due to its remarkable success in targeting hematological malignancies. Unfortunately, CAR-T cell immunotherapy has not had the same amount of success in solid tumors due to the challenging tumor's immunosuppressive microenvironment. Therefore, we hypothesize the use of macrophages as a vessel for CAR immunotherapy due to their associate with tumors as TAMs and also the tumors ability to secrete various chemokines that can attract myeloid cells to the tumor site. THP-1 a monocytic cell line that represents a monocyte/macrophage model was transduced with an anti-CD19 scFv CAR construct. K562 a leukemia cell line that represents hematological malignancies and H460 a lung cancer cell line that represents solid tumors were transduced to overexpress the surface marker CD19. THP-1 clones expressing the anti-CD19 CAR construct were cocultured with the two tumor cell lines, which demonstrated the ability of the THP-1 CARs to specifically targeted and lysis the tumor cells that overexpressed the CD19 surface marker. Upon CAR activation, THP-1 cells were polarized towards the M1 classical activated phenotype due to the increase in expression of TNF-[alpha], IL-1[beta], IL-6, IL-12[beta], CXCl10, HLA-DR, and CD86. Additionally, THP-1 cells did not show any change in the M2 alternative activated markers of IL10, TFG[beta], CCL18, CCL22, CD206, and CD204 to suggest polarization towards the M2 phenotype. As a result, this study validates the proof of concept that macrophages could potentially be a vessel for CAR immunotherapy.

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.

Targeting the Disialoganglioside GD2 with Chimeric Antigen Receptor T Cells for Immunotherapy in Diffuse Midline Gliomas and Exploration of Neuron opc Synaptic Connectivity in the Context of Adaptive Myelination

Targeting the Disialoganglioside GD2 with Chimeric Antigen Receptor T Cells for Immunotherapy in Diffuse Midline Gliomas and Exploration of Neuron opc Synaptic Connectivity in the Context of Adaptive Myelination Book
Author : Christopher Mount
Publisher : Unknown
Release : 2020
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Histone 3 K27M mutated diffuse midline glioma (H3K27M DMG) is a universally fatal pediatric brain tumor. Despite improved understanding of the molecular origins of this disease, translations to improvement in clinical outcomes have yet to materialize. To date, there has been little target exploration for immunotherapy applications in H3K27M DMG. In this thesis, I describe my work that elucidated substantial preclinical efficacy of chimeric antigen receptor (CAR)-bearing T cells targeting the disialoganglioside GD2 as an immunotherapy regimen in patient-derived orthotopic xenograft models of H3K27M DMG. Single-dose systemic administration of GD2-4-1BB-CAR T cells in multiple orthotopic xenograft models of H3K27M DMG achieves potent and lasting antitumor efficacy, including tumor clearance by in vivo bioluminescence imaging and follow-up histology. Treatment-associated toxicity was transient and generally tolerated during the period of peak anti-tumor activity in brainstem orthotopic xenografts. If these results are predictive of human response, GD2-directed CAR T cell therapy in the setting of careful clinical management could have a transformative impact upon H3K27M DMG outcomes. In part two of this thesis, I present data revealing a brain-wide map of afferent neuronal connectivity to oligodendrocyte precursor cells (OPCs). Neurons form bona fide synapses with oligodendrocyte precursor cells (OPCs), but the circuit context of these neuron to OPC synapses remains incompletely understood. Using monosynaptically-restricted rabies virus tracing of OPC afferents, I identified extensive afferent synaptic inputs to OPCs residing in secondary motor cortex and underlying corpus callosum of adult mice. These inputs primarily arise from functionally-interconnecting cortical areas and thalamic nuclei, demonstrating that OPCs in motor-associated territories have synaptic access to brain-wide projection networks engaged in planning and execution of motor tasks. This circuit map is a foundational tool for future studies of context-specific neuron-OPC synapse function.

Fast Facts CAR T Cell Therapy

Fast Facts  CAR T Cell Therapy Book
Author : Richard J. Buka,Ankit J. Kansagra
Publisher : Karger Medical and Scientific Publishers
Release : 2021-02-28
ISBN : 3318067415
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

Genome Engineering to Expand Applications of Human T cell Immunotherapy

Genome Engineering to Expand Applications of Human T cell Immunotherapy Book
Author : Alexandra E. Grier
Publisher : Unknown
Release : 2017
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Adoptive T-cell therapy, particularly chimeric antigen receptor (CAR) therapy, is a revolutionary and quickly-evolving means of treating cancer patients who can no longer be helped by standard therapies. In multiple clinical trials, including our own at Seattle Children’s Hospital, CD19 CAR therapy for B-cell leukemia and lymphoma has achieved a complete remission rate of >90%. Unfortunately, in its present form, CAR therapy has had limited success against solid tumors. It is also not currently an option for patients who lack sufficient numbers of their own T-cells due to their disease or prior treatments. Thus, genome engineering strategies to overcome these limitations could be of great benefit to patients. We chose a two-pronged approach to achieve this goal: knock-out of the endogenous TCR and multiplex knock-out of the T-cell inhibitory checkpoints PD-1, Tim3, Lag3, and TIGIT. Knocking out these inhibitory checkpoint proteins specifically in the CAR T-cells will maintain the synergistic effects recently seen in combination monoclonal antibody therapy without the serious, sometimes fatal, immune-mediated side effects seen with systemic antibody therapy. To this end, we first developed a linear mRNA expression vector with a long, encoded poly(A) tail to allow transient delivery of nucleases such as TALENs or CRISPR to primary human cells in a consistent, clinically applicable, and scalable fashion. We then used IVT mRNA made from this vector to deliver a TALEN pair targeting the TCR locus to CD19 CAR T-cells, and demonstrated that removal of the endogenous TCR does not hinder CAR T-cell function in vitro or in vivo in a murine xenograft tumor model. Knockout of the endogenous TCR will facilitate production of an allogeneic CAR T-cell product to be used as a bridge to HSCT in patients who cannot receive autologous CAR therapy. Removal of the endogenous TCR will also add a measure of safety when creating CAR T-cells lacking inhibitory checkpoint proteins by preventing GvHD while retaining anti-tumor effects. These technologies and methods may allow a wider variety of patients to benefit from the recent advances in CAR T-cell therapy.

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.

Williams Hematology 10th Edition

Williams Hematology  10th Edition Book
Author : Kenneth Kaushansky,Marshall A. Lichtman,Josef T. Prchal,Marcel M. Levi,Linda J. Burns
Publisher : McGraw Hill Professional
Release : 2021-01-14
ISBN : 126046413X
Language : En, Es, Fr & De

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Book Description :

The landmark text that has guided generations of hematologists and related practitioners―updated with the latest research findings and improved format and presentation Long revered for its comprehensiveness and extraordinary depth of detail, Williams Hematology provides essential coverage of the origins, pathophysiological mechanisms, and management of benign and malignant disorders of blood and marrow cells and coagulation proteins. The text contains a wealth of basic science and translational pathophysiology for optimal, lifelong learning. Experts in research and clinical hematology, the editors are known worldwide for their contributions to the field. This new edition contains everything that has made Williams Hematology the go-to resource for decades and has been updated with new chapters and critical new research into the molecular mechanisms responsible for hematological disorders and the impact on diagnosis and treatment. And the new format enables you to access each chapter via content modules covering key topics, with summaries, infographics, and cases―all linked to review questions for self-assessment. The full-color presentation integrates images of blood and tissue findings where they are cited in the text. NEW TO THIS EDITION: Updated and revised content reflecting the latest research and developments Convenient format that streamlines the learning process and improves retention Additional chapters added on: Immune Checkpoint Inhibitors Immune Cell Therapy: Chimeric Antigen Receptor T Cell Therapy Immune Cell Therapy Dendritic Cell and Natural Killer Cell Therapy The processes of cell death and survival Application of Big Data and Deep Learning in Hematology Williams Hematology Cases with multiple-choice questions including detailed explanations—perfect preparation for the boards Continuously updated online content with comprehensive drug therapy database and other resources

Dual Transgenesis of T Cells with a CD44v6 specific Chimeric Antigen Receptor and a Suicide Gene for the Safe Eradication of Chemoresistant Leukaemia and Myeloma

Dual Transgenesis of T Cells with a CD44v6 specific Chimeric Antigen Receptor and a Suicide Gene for the Safe Eradication of Chemoresistant Leukaemia and Myeloma Book
Author : Monica Casucci
Publisher : Unknown
Release : 2012
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Download Dual Transgenesis of T Cells with a CD44v6 specific Chimeric Antigen Receptor and a Suicide Gene for the Safe Eradication of Chemoresistant Leukaemia and Myeloma book written by Monica Casucci, available in PDF, EPUB, and Kindle, or read full book online anywhere and anytime. Compatible with any devices.

Endogenous Leukocyte Activation by Chimeric Antigen Receptor T Cell Immunotherapy

Endogenous Leukocyte Activation by Chimeric Antigen Receptor T Cell Immunotherapy Book
Author : Paul Spear
Publisher : Unknown
Release : 2013
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Many protocols for adoptive T cell therapy (ACT) include preparative conditioning strategies to deplete host lymphocytes prior to T cell infusion. Total body irradiation and high-dose chemotherapy regimens not only relieve immunosuppression, but increase persistence of the transferred T cells in the host. These preconditioning regimens appear to correlate with improved clinical responses following adoptive T cell therapy. However, they can also result in the death of healthy cells and reduce the quality of life for patients. In addition, some clinical trials employing host conditioning strategies in combination with adoptive T cell transfer have demonstrated tumor persistence and relapse as a result of the outgrowth of antigenic variants. Harnessing endogenous lymphocytes is one method to broaden the tumor-specific T cell repertoire and eliminate tumor cells that have lost the targeted antigen following adoptive T cell therapy. Recent evidence suggests that transferred T cells may eradicate tumors without the need for prior conditioning, indicating that T cell therapies can enhance tumor elimination by relieving immunosuppression and promoting endogenous immunity. Collectively, the data presented in this thesis challenge the popular paradigm that lymphodepleting regimens are crucial for optimal efficacy of all ACTs. NKG2D chimeric antigen receptor (CAR) T cell therapy mounted robust anti-tumor immunity in unconditioned (immune intact) hosts, and this therapy harnessed endogenous macrophage and T cell anti-tumor immunity for superior elimination of ovarian tumors. Moreover, these data suggest that endogenous immunity broadens the specificity of the anti-tumor immune response and is critical for the control of antigenic tumor variants. The data also elucidate unique effector mechanisms employed by the transfused CD8 and CD4+ T cells in awakening endogenous macrophage and T cell immunity. These findings advance the T cell therapy field by improving the understanding of the mechanisms that are required for effective adoptive T cell therapy in unconditioned patients.

The Basic Science of Oncology Sixth Edition

The Basic Science of Oncology  Sixth Edition Book
Author : Lea Harrington,Robert E. Bristow,Ian F. Tannock,Richard Hill
Publisher : McGraw Hill Professional
Release : 2021-01-08
ISBN : 1259862089
Language : En, Es, Fr & De

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Book Description :

Complete coverage of the basis of cancer and molecular biology – from globally recognized experts The Basic Science of Oncology is an accessible and thorough introduction to cancer causation, cancer biology, and the biology underlying cancer treatment. You’ll find everything you need to know about the latest critical thinking in oncology, as well ready to apply information about state-of-the-art science and therapeutic applications. Written by leading oncology researchers and clinicians, this is an essential resource for health professionals, students, advanced undergraduates and graduates in biological sciences, and clinicians needing an understanding of cancer cells. Presented in full-color, The Basic Science of Oncology reflects the latest research and developments in the field. Features NEW chapters: Epigenetics and Principles of Genome Regulation and Targeted Cancer Diagnosis and Treatment Thoroughly revised content, with expanded coverage of key topics such as immune system and immunotherapy, tumor growth and metabolism, vaccine development, methods of molecular analysis, tumor environment, and more The most current, evidence-based oncology primer—one that encapsulates the science of cancer causation, cancer biology, and cancer therapy Key insights into molecular and genetic aspects of cancer familiarize you with cancer biology as applied to prognosis and personalized cancer medicine In-depth focus on the discovery, evaluation, and biology of anti-cancer drugs, immunotherapy, and molecularly-targeted agents Up-to-date coverage of the basic science of radiation therapy

Cancer Immunotherapy

Cancer Immunotherapy Book
Author : Eric Hans Gschweng
Publisher : Unknown
Release : 2015
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Engineering the immune system against cancer ideally provides surgical precision against the antigen bearing target cell while avoiding the systemic, off-target toxicity of chemotherapy. Successful treatment of patients in the clinic has been achieved by the expression of anti-cancer T-cell receptors (TCR) and chimeric antigen receptors (CAR) in T cells followed by infusion of these cells into cancer patients. Unfortunately, while many patients initially respond showing anti-tumor efficacy, the effects are by and large transient with the majority of patients succumbing to disease. This observation speaks to the power of the engineered antigen receptor, but also indicates a need for a persistent source of cells to mount a continuous response. This thesis work sought to investigate the feasibility of engineering immunity using hematopoietic stem cells (HSC). HSC are at the top of the hematopoietic hierarchy, and would theoretically provide a continuous supply of antigen receptor bearing T cells capable of eliminating disease in a patient. Important considerations for using HSCs in gene therapy include: efficient gene delivery to HSCs which are refractory to gene modification by nature, robust expression of the transgene within gene modified cells to provide efficacy, evaluation of successful gene modification and engraftment following transplant, the ability of gene modified T cells to mount an immune response against their intended targets, and the ability to eliminate the gene modified cells in the event of undesired outcomes. Current systems to study human HSC biology and gene therapy are limited, and the best available are human / mouse chimeric transplant systems. Using these models, we evaluated the utility of positron emission tomography (PET) in the humanized mouse following transplant of gene modified cells, and found it superior to peripheral blood flow cytometry in being able to temporally establish successful engraftment. Using a lentiviral vector expressing both a TCR against a common cancer / testes antigen, NY-ESO-1, as well as a PET imaging / suicide gene, we demonstrated the ability to monitor engraftment, successful generation of effector cells capable of killing patient derived cancer cell lines, and the complete elimination of gene modified cells. This final work provides support for a clinical trial soon to enroll patients at UCLA. The use of HSCs for engineered cancer immunotherapy could overcome current limitations associated with the lack of persistence of engineered terminally differentiated immune cells. Further, the rich clinical history of gene therapy using HSCs provides a broad platform for future studies aimed at the broad spectrum of cancer disease.

Hematopoietic Stem Cell derived Chimeric Antigen Receptor Expressing Cells Traffic to HIV Reservoir Sites in SHIV infected Non human Primates

Hematopoietic Stem Cell derived Chimeric Antigen Receptor Expressing Cells Traffic to HIV Reservoir Sites in SHIV infected Non human Primates Book
Author : Isaac M. Barber-Axthelm
Publisher : Unknown
Release : 2019
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

The successful treatment of 2 HIV+ individuals with allogeneic stem cell transplantations has garnered much interest in its utility as a therapy for HIV. However, there are significant limitations that prevent allogeneic stem cell transplantation from being a viable therapy for HIV infection, including toxicity due to Graft-versus-host disease, and the limited availability of donors who are homozygous for the CCR5[delta]32 mutation. One viable option to circumvent these limitations and provide a functional cure, through immune-mediated elimination of the virus, is with chimeric antigen receptor (CAR) immunotherapy. By introducing the CAR engineered to target HIV infected cells into hematopoietic stem cells, we have the potential to generate a self-renewing population of CAR T-cells, thus circumventing some of the limitations with longevity that are seen with CAR T-cells. Here, we report trafficking of hematopoietic stem and progenitor (HSPC)-derived CAR+ cells to HIV tissue reservoir sites, in a pigtail macaque model of HIV infection. CAR+ cells were identified in the lymphoid germinal centers, the parenchyma of the central nervous system, and the gastrointestinal tract by immunohistochemistry, almost 2 years after initial engraftment with lentiviral modified HSPCs. Multilineage engraftment of CAR+ cells were identified in lymphoid germinal centers and the gastrointestinal tract, consisting of T-cells, B-cells, and myeloid lineage cells. CAR+ B-cells in the germinal centers were also actively replicating, characterized by robust Ki-67 expression. No difference was observed in trafficking, engraftment, and cell cycle activity between CAR animals and control animals that carry a "tailless" CAR which lacks the cytoplasmic signal transduction domain. These results show the HSPC-derived CAR+ cells will traffic to, and persist in, HIV tissue reservoir sites, with multilineage engraftment of CAR+ cells. The method could be used as a platform for immunotherapeutic delivery treatment of HIV infection, as well as a variety of other medical conditions.