BMS 545 Immunology Lecture (PDF)

WELCOME! BMS 545 IMMUNOLOGY OCTOBER 9, 2023  OBJECTIVES Upon completion of this case students should be able to:  Describe the typical interaction between T cells & antigen-presenting cells.  Explain the domains of chimeric antigen receptors (CARs) & their respective functions.  Explain how...

WELCOME! BMS 545 IMMUNOLOGY OCTOBER 9, 2023  OBJECTIVES Upon completion of this case students should be able to:  Describe the typical interaction between T cells & antigen-presenting cells.  Explain the domains of chimeric antigen receptors (CARs) & their respective functions.  Explain how CARs allow T cells to interact with and attack both cancer cells and normal cells.  Apply knowledge of the immune system to current applications of cancer immunotherapies.  Understand side effects of immunotherapy treatment and compare this treatment with typical chemotherapy.  CAR T CELL THERAPY  A type of treatment in which a patient's T cells are changed in the laboratory so they will attack cancer cells  T cells are taken from a patient’s blood & the gene for a special receptor called a chimeric antigen receptor (CAR) that binds to a certain protein on the patient’s cancer cells is added to T cells in the lab  Large numbers of the CAR T cells are grown in the lab & given to the patient by infusion  CAR T-cell therapy is used to treat certain blood cancers, & is being studied in treatment of other types of cancer  WHAT ARE CAR T-CELLS?!  Combination of severali mmune protein domains (hence the term “chimeric”)  Made up of: 1. Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker  Heavy & light chain region of anti-CD19 immunoglobulin 2. Transmembrane portion of CD28 3. CD3 zeta proteins (with ITAMs)  In this specific case study, we are using CAR T cells to target CD19 on B cells  CD19  Cluster of Differentiation 19  Part of the B cell co-receptor complex  A cell marker of normal AND neoplastic B cells  Critically involved in establishing intrinsic B cell signaling thresholds through modulating both B cell receptor- dependent & independent signaling  Target of CAR-T Cell therapy for chronic lymphocytic leukemias  It most often arises from a malignant clone of B cells MEMORY CAR T CELLS CURRENT USES OF CAR T CELL THERAPY  CO-STIMULATORY SIGNALING DOMAINS HAVE BEEN ADDED TO NEWER GENERATIONS OF CAR T CELLS TO IMPROVE THEIR ABILITY TO PRODUCE MORE T CELLS AFTER INFUSION AND SURVIVE LONGER IN THE CIRCULATION.