مبانی ایمنی‌درمانی با گیرنده‌های آنتی‌ژن کایمریک (CAR)

__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. Basics of Chimeric Antigen Receptor (CAR) Immunotherapy Copyright Preface References 1. An Introduction to CAR Immunotherapy Immunotherapy: Historical Perspective Concepts That Led to the Development of CAR-Based Immunotherapy Against Cancers Immune Escape Through Disruption of Antigen Presentation and Costimulation Immune Escape Through T-Cell Exhaustion Tolerance as a Major Immune Escape Mechanism Loss of Tumor Immunogenicity Immune Tolerance: A Natural Checkpoint Protecting Cancers From Immune Recognition and Eradication References 2. Components and Design of Chimeric Antigen Receptors Prototypical Design of Chimeric Antigen Receptors CAR Ectodomain Significance of Choosing Antibody Domains (CARbodies) for the CARs Choice of Hinges Supporting scFvs Choice of CAR Transmembrane Domains Choice of CAR Endodomains and Costimulatory Molecules References 3. scFv Cloning, Vectors, and CAR-T Production in Laboratory for Preclinical Applications Advantages of Using scFv Over Full-Length Monoclonal Antibody in CAR Therapy Choices of Tumor Antigens, the Molecular Biology Techniques Used to Generate and Test Tumor Antigen-Specific scFvs scFv Generation Using Hybridoma scFv Screening Through Phage Display Technology Generating Chimeric Gene Sequences for Cloning Into Retroviral Vectors Retroviral Vectors Used for Cloning CAR Chimeric Genes Retroviral Packaging System for CAR Production Transposon-Based System for CAR Cloning and Expression Vectors Used for CAR Production Protocol for CAR Production in Laboratory Settings for Preclinical Applications Production of Third-Generation CAR Lentiviral Particles Materials Protocol 1 Protocol 2 Protocol 3 Day 0 Day 2 Day 3 Expansion of Primary T Cells and Generation of CAR-Modified T cells In Vitro Testing of CAR-T Cells Measuring tumor-killing activity In Vivo Testing of CAR-T Cells References 4. Production of CAR-T Cells for Clinical Applications Clinical Production of CAR-T Cells Using Good Manufacturing Practices Patient Recruitment and Eligibility Criteria for Receiving CAR T-Cell Therapy Eligibility Criteria for CD19+ B-Cell Malignancies Eligibility Criteria for CAR-T Therapy in Patients With Solid Cancers, e.g., TAG72+ Metastatic Colorectal Cancer, and FR+ O ... Leukapheresis and Patient T-Cell Isolation The Leukapheresis Activation and Expansion of PBMCs Generation of CAR-T Cells Lentiviral Transduction Lentiviral transduction in CD3/CD28 bead-activated T cells Retroviral transduction in OKT3-activated T cells Infusion of CAR-T Cells Patient Monitoring After T-Cell Infusion Adverse outcome Response evaluation in solid cancers Tumor burden in B-cell malignancies and response evaluations Other techniques used to assess tumor responses to CAR-T therapy References 5. Challenges and Opportunities to Improve CAR T-Cell Therapy CAR T-Cell Exhaustion Controlling Antigen Escape in CAR-T Cells Monitoring CAR-T Persistence In Vivo Toxicities Associated With CAR Therapy and Management of Those Toxicities The Cytokine Release Syndrome On-Target/Off-Tumor Toxicity Allogeneic CARs References Index A B C D E F G H I J L M N O P R S T Z 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