CAR-T-Cell-Based-Immunotherapy-Basic-Principles

CAR-T CELL-BASED IMMUNOTHERAPY BASIC PRINCIPLES The basic design of CAR 1 Structural and Functional Basis of CAR includes a tumor-associated antigen (TAA) binding region VL Anti-tumor signal Tumor antigen (usually scFv), an extracellular Antigen-binding hinge region, a transmem- VH region (scFv) brane region and an intracel- lular signal. The first chimeric Monoclonal Hinge region TCR was constructed by antibody replacing the Vα and Vβ extra- cellular domains of the TCR TCR-CD3 Transmembrane T cell Tumor cell chains. Single chain antibody complex region links the CD3ζ for the first γε αβ εδ ζ ζ Cell activation generation. Costimulatory Signal transduction Cytotoxicity induction molecule, such as CD28, has region Cytokine production been engineered to the signal Cell survival transduction region for the Cell proliferation second generation. Another costimulatory molecule based 2 Evolution of CAR on the second generation for the third generation has been Seminal research 1993 2nd-generation 2007 4th-generation engineered to the signal 3rd-generation 2009 transduction region. The 1989 1st-generation 1998 2003 2004 cytokines based on the second generation for the VH VL fourth generation has been engineered to the signal γε α β εδ ζ ζ transduction region. CD3ζ CD8α CD4 A dual CAR T cell expresses two separate CARs with differ- CD28 4-1BB Hinge Cytokine ent ligand binding targets. Dual CAR T cell activation IgG1 sequences Transgene Co-stimulating ligand requires co‑expression of both targets on the tumour. A 3 New CAR Models and Concepts conditional CAR T cell is by default unresponsive until the Classic Dual Conditional Tandem Physiological Universal Marked addition of a small molecule CAR CAR CAR CAR CAR CAR CAR to complete the circuit. A tandem CAR T cell expresses a 2 12 12 2 2 2 single CAR consisting of two 1 1 1 1 linked scFvs that have differ- ＋ ＋ ent affinities. The physiologi- ＋ ＋ ＋ ＋ cal CAR consists of an antigen receptor and a CD3ζ intracel- Additional small Receptor Avidin/anti-FITC Biotin/FITC Selection marker lular signaling domain molecule & ligand labeled scFv with/without a transmem- brane and a spacer region. The WHAT WE DO: universal CAR utilizes biotin or anti-FITC scFv as targeting One-Stop CAR-T Therapy Development Services Products: region fused with the trans- TCR Modified T Cell Development Services Diseases Associated Antigen membrane domain. Marked TCR-Like Antibody Services CAR Vector System CAR T cells express a CAR plus Dendritic Cell Vaccine Development Services Viral Particle a tumour epitope to which an Bispecific TCR Development Service CAR/TCR Development Kits existing monoclonal antibody agent binds. Creative Biolabs CAR/TCR-related Products & Services Copyright © 2018 Creative Biolabs. All Rights Reserved. | Contact Us