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The vector of anti-TAF1 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human TAF1. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-TAF1 antibody linked to CD28 and CD3ζ signaling domains. And the vector product was designed for the treatment of Breast cancer.
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Details
Target
TAF1
Epitope
aa 1784-1894
Targeting Cell Type
T cell
Targeting Diseases
Breast cancer
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
1E11
Host
Mouse
Target Species
Human
Gene Name
TAF1 Gene(Protein Coding) TATA-Box Binding Protein Associated Factor 1
TATA-Box Binding Protein Associated Factor 1; TAF1 RNA Polymerase II, TATA Box Binding Protein (TBP)-Associated Factor, 250kDa; TBP-Associated Factor 250 KDa; Cell Cycle Gene 1 Protein; EC 2.7.11.1; TAF(II)250; TAFII-250; TAFII250; TAF2A; P250; BA2R; CCG1; CCGS; TATA Box Binding Protein (TBP)-Associated Factor, RNA Polymerase II, A, 250kD; Transcription Initiation Factor TFIID 250 KDa Subunit; Transcription Initiation Factor TFIID Subunit 1;
Introduction
Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor TFIID, which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. TAF1 is the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. TAF1 also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. TAF1 contains two independent protein kinase domains at the N- and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Mutations in TAF1 result in Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder.
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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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