医学免疫学课件：CAR-T免疫疗法.pptxVIP

A brief introduction to Chimeric Antigen Receptor T Cell Immunotherapy ;Outline;CAR ACT TIL scFv TCR TAA ALL/CLL ITAM PTK;Definition - Activate the immune cells to clear the cancer focus or significantly inhibit the tumor proliferation. Immuno-surveillance - Elimination, Equilibration, Escape Classification - Non-specific · Checkpoint blocking · Immune cell activation - Specific · Tumor vaccination · Adoptive cell transfer therapy (ACT);? Ectodomain - Signal peptide - Antigen recognition region - Spacer ? Transmembrane domain ? Endodomain;2. Structure of CAR;Depiction of 3 generations of CARs by Monica Casucci and Attilio Bondanza - /v02p0378.htm. Licensed under Public Domain via Commons;3.1 Targeting 3.2 Signaling 3.3 Trafficking 3.4 Persistence 3.5 Function 3.6 Toxicity;Find the right antigen (TAA) - CD19, CD20, PSMA, HER-2/neu, CAIX Choose a good receptor - scFv, anti-VEGFR2, anti Her3/4 receptor - NKG2D receptor, anti IL-13 receptor - Anti FITC receptor (multiple targeting) Increase recognition affinity (accuracy)? - Activation is independent of affinity - High affinity - inhibit multiple binding - Low affinity - avoid “on target – off tumor” effect;Signal 1 (Activation) - Antigen presenting (MHC - TCR) Signal 2 (Survival) - Co-stimulator (B7.1/7.2 - CD28) Signal 3 (Differentiation) - Cytokines (DC - receptor);3.2 Signaling;T-cell;Urba WJ, longo DL. N engl J med 2011;365:754-757.;3.2 Signaling;蛋白酪氨酸激酶Lck或Fyn活化;3.2 Signaling;3.1 Targeting 3.2 Signaling 3.3 Trafficking 3.4 Persistence 3.5 Function 3.6 Toxicity;3.1 Targeting 3.2 Signaling 3.3 Trafficking 3.4 Persistence 3.5 Function 3.6 Toxicity;Use of conditioning chemotherapy Patient tumor burden Cytokine supplementation Co-stimulatory signaling T cell phenotype Use of viral specific T cells …………;3.1 Targeting 3.2 Signaling 3.3 Trafficking 3.4 Persistence 3.5 Function 3.6 Toxicity;3.1 Targeting 3.2 Signali