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Engineered T Cell Therapy for Cancer in clinics (CAR-T Cell Therapy…
Engineered T Cell Therapy for Cancer in clinics
Introduction
microenvironment of solid tumor
fibrous matrix
immunosupressive cells
immune checkpoint receptors of tumor cells
traditional methods
surgical resection
radiotherapy
chemotherapy
small molecule targed drugs
mAbs
HSC transplantation
IT
PD-1 and PD-L1 checkpoint inhibitors
anti-CD19 CAR-T cell therapy
TCR-T Cell Therapy
success
hematological maligancies
solid tumors
differences
TCR-T
recognize polypeptides presented by MHC
recognize intracellular Ag
wider range of target
CAR-T
use Ab fragments bind to specific Ag
recognize cell surface protein
smaller range of target
CAR-T Cell Therapy
progress
isolate T cells from patients
modified T cells with CARs
stimulate and expand CAR-T cells
transfuse CAR-T cells back to patients
monitor patients
success
failures
CRS
neurotoxicity
on-target-off-tumor toxicity
exhaustion of CAR-T cells
tumor excape
treatment for solid tumors
cost
encephaledema
hematological malignancies
CD19
CD20
CD22
BCMA
solid tumors
high heterogenity
tumor Ag express on normal cells
future
dual CAR-T cells
to secrete proinflammatory cytokines
immune checkpoint inhibitor
component
extracellular domain (scFv): VH and VL
recognize specific tumor Ag
not MHC restricted
hinge domain
signal transduction
Ig superfamily: CD8, CD28, IgG
intracellular domain
CD3 chain of TCR
co-stimulatory molecules: CD28 or CD137 (4-1BB)
cell proliferation
survial time
cytokine secretion
DIscussion
CTL-->memory T cells
long-term immune memory
other field
infectious diseases
organ tranasplantation
autoimmune diseases
other cells type
pluripotent stem cells
hematopoietic stem cells
NK cells