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The vector of anti-LDLRAP1 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human LDLRAP1. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-LDLRAP1 antibody linked to CD28 and CD3ζ signaling domains. And the vector product was designed for the treatment of Glioma.
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Details
Target
LDLRAP1
Epitope
aa 1-264
Targeting Cell Type
T cell
Targeting Diseases
Glioma
Generation
Second
Vector Name
pCDCAR1
Vector Length
~8kb
Vector Type
Lentiviral vector
Receptor Construction
scFv-CD28-CD3ζ
Discription of Signaling Cassetes
CD28 CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatorysignals required for T cell activation and survival. CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins which are expressed on antigen-presenting cells(APC). CD28 modulates the primary TCR/CD3ζ signal in a different fashion than the late costimulatory elements OX40 and 4-1BB. CD28 enhances the expression of downstream regulators that impact on T-cell proliferation, death, differentiation, and effector functions. CAR+ T cells containing the CD28 endodomain showed strikingly enhanced sustained T cell activation, growth, survival. And CD28 results in a brightly expressed, stable receptor as the transmembrane domain. Including CD28 costimulatory domains in CARs led to enhanced anti-malignancy efficacy. CD3ζ CD3ζ, also known as T-cell receptor zeta, which together with T-cell receptor and CD3γ, δ , ε chain, forms the TCR-CD3 complex. ζ was expressed independently from the complex. The zeta chain plays an important role in coupling antigen recognition to several intracellular signal-transduction pathways. CD3-zeta,which contains 3 ITAMs, is the most commonly used endodomain component of CARs. It transmits an activation signal to the T cell after antigen is bound. CD3-zeta may not provide a fully competent activation signal and additional co-stimulatory signaling is needed. For example, chimeric CD28 and OX40 can be used with CD3-zeta to transmit a proliferative/survival signal, or all three can be used together.
Target
Clone
4G4-D5
Host
Mouse
Target Species
Human
Gene Name
Low Density Lipoprotein Receptor Adaptor Protein 1
LDLRAP1 is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. Diseases associated with LDLRAP1 include Hypercholesterolemia, Autosomal Recessive and Homozygous Familial Hypercholesterolemia. Among its related pathways are Lipoprotein metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include phosphatidylinositol-4,5-bisphosphate binding and amyloid-beta binding. An important paralog of this gene is NUMBL.Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface. Required for trafficking of LRP2 to the endocytic recycling compartment which is necessary for LRP2 proteolysis, releasing a tail fragment which translocates to the nucleus and mediates transcriptional repression (By similarity).
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For research use only. Not intended for any clinical use. No products from Creative Biolabs may be resold, modified for resale or used to manufacture commercial products without prior written approval from Creative Biolabs.
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