CAR-T CELL-BASED IMMUNOTHERAPY BASIC PRINCIPLES
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Copyright © 2018 Creative Biolabs. All Rights Reserved. Email: [email protected] Tel: 1-631-381-2994 CAR-T CELL-BASED IMMUNOTHERAPY BASIC PRINCIPLES The basic design of CAR includes a tumor-associated antigen (TAA) binding region (usually scFv), an extracellular hinge region, a transmem- brane region and an intracel- lular signal. The first chimeric TCR was constructed by replacing the Vα and Vβ extra- cellular domains of the TCR chains. Single chain antibody links the CD3ζ for the first generation. Costimulatory molecule, such as CD28, has been engineered to the signal transduction region for the second generation. Another costimulatory molecule based on the second generation for the third generation has been engineered to the signal transduction region. The cytokines based on the second generation for the fourth generation has been engineered to the signal transduction region. A dual CAR T cell expresses two separate CARs with differ- ent ligand binding targets. Dual CAR T cell activation requires co‑expression of both targets on the tumour. A conditional CAR T cell is by default unresponsive until the addition of a small molecule to complete the circuit. A tandem CAR T cell expresses a single CAR consisting of two linked scFvs that have differ- ent affinities. The physiologi- cal CAR consists of an antigen receptor and a CD3ζ intracel- lular signaling domain with/without a transmem- brane and a spacer region. The universal CAR utilizes biotin or anti-FITC scFv as targeting region fused with the trans- membrane domain. Marked CAR T cells express a CAR plus a tumour epitope to which an existing monoclonal antibody agent binds. Creative Biolabs CAR/TCR-related Products & Services Evolution of CAR 2 New CAR Models and Concepts 3 Structural and Functional Basis of CAR 1 Antigen-binding region (scFv) Monoclonal antibody V H V H V L V L TCR-CD3 complex Hinge region Tumor cell Anti-tumor signal Tumor antigen T cell γ ε α β ε δ ζ ζ Transmembrane region Signal transduction region Cell activation Cytotoxicity induction Cytokine production Cell survival Cell proliferation CD8α CD4 CD28 Receptor & ligand Additional small molecule Avidin/anti-FITC labeled scFv Biotin/FITC Selection marker Hinge IgG1 sequences Co-stimulating ligand Transgene Cytokine 4-1BB 1989 1993 1998 2003 2004 2007 2009 CD3ζ Classic CAR Dual CAR Tandem CAR Physiological CAR Universal CAR Marked CAR Seminal research 1st-generation 2nd-generation 3rd-generation 4th-generation ＋ 1 2 ＋ 1 2 ＋ 1 2 ＋ 1 2 ＋ 1 2 Conditional CAR ＋ 1 2 γ ζ ζ α β ε ε δ WHAT WE DO: Products: Diseases Associated Antigen CAR Vector System Viral Particle CAR/TCR Development Kits One-Stop CAR-T Therapy Development Services TCR Modified T Cell Development Services TCR-Like Antibody Services Dendritic Cell Vaccine Development Services Bispecific TCR Development Service
Transcript of CAR-T CELL-BASED IMMUNOTHERAPY BASIC PRINCIPLES
Copyright © 2018 Creative Biolabs. All Rights Reserved. Email: [email protected] Tel: 1-631-381-2994
CAR-T CELL-BASED IMMUNOTHERAPYBASIC PRINCIPLES
The basic design of CAR includes a tumor-associated antigen (TAA) binding region (usually scFv), an extracellular hinge region, a transmem-brane region and an intracel-lular signal. The first chimeric TCR was constructed by replacing the Vα and Vβ extra-cellular domains of the TCR chains. Single chain antibody links the CD3ζ for the first generation. Costimulatory molecule, such as CD28, has been engineered to the signal transduction region for the second generation. Another costimulatory molecule based on the second generation for the third generation has been engineered to the signal transduction region. The cytokines based on the second generation for the fourth generation has been engineered to the signal transduction region.
A dual CAR T cell expresses two separate CARs with differ-ent ligand binding targets. Dual CAR T cell activation requires co‑expression of both targets on the tumour. A conditional CAR T cell is by default unresponsive until the addition of a small molecule to complete the circuit. A tandem CAR T cell expresses a single CAR consisting of two linked scFvs that have differ-ent affinities. The physiologi-cal CAR consists of an antigen receptor and a CD3ζ intracel-lular signaling domain with/without a transmem-brane and a spacer region. The universal CAR utilizes biotin or anti-FITC scFv as targeting region fused with the trans-membrane domain. Marked CAR T cells express a CAR plus a tumour epitope to which an existing monoclonal antibody agent binds.
Creative BiolabsCAR/TCR-relatedProducts &Services
Evolution of CAR2
New CAR Models and Concepts3
Structural and Functional Basis of CAR1
Antigen-bindingregion (scFv)
Monoclonalantibody
VH
VH
VL
VL
TCR-CD3complex
Hinge region
Tumor cell
Anti-tumor signal Tumor antigen
T cell
γ ε α β ε δζζ
Transmembraneregion
Signal transductionregion
Cell activationCytotoxicity inductionCytokine productionCell survivalCell proliferation
CD8α CD4
CD28
Receptor& ligand
Additional smallmolecule
Avidin/anti-FITClabeled scFv Biotin/FITC Selection marker
Hinge
IgG1 sequences Co-stimulating ligandTransgene
Cytokine4-1BB
1989
1993
1998 2003 2004
2007
2009
CD3ζ
ClassicCAR
DualCAR
TandemCAR
PhysiologicalCAR
UniversalCAR
MarkedCAR
Seminal research1st-generation
2nd-generation3rd-generation
4th-generation
＋1
2
＋1
2
＋1
2
＋1
2
＋1 2
ConditionalCAR
＋1 2
γ ζζα βε ε δ
WHAT WE DO:Products:Diseases Associated AntigenCAR Vector SystemViral Particle CAR/TCR Development Kits
One-Stop CAR-T Therapy Development Services TCR Modified T Cell Development ServicesTCR-Like Antibody Services Dendritic Cell Vaccine Development ServicesBispecific TCR Development Service
