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pCDCAR7 ERBB2×EGFR h(ζ/28ICOS) (CAR-LC366)

The vector of anti-HER2×EGFR chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target human HER2 and EGFR. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-HER2 antibody linked to CD3ζ signaling domain, and scFv of anti-EGFR antibody linked to CD28 and ICOS signaling domains. And the vector product was designed for the treatment of glioblastoma.

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Details

  • Target
  • HER2
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Glioblastoma
  • Generation
  • Third
  • Vector Name
  • pCDCAR1
  • Vector Length
  • ~8kb
  • Vector Type
  • Lentiviral
  • Discription of Signaling Cassetes
  • CD28
    CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals 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.
    ICOS
    ICOS, it enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. ICOS does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. It prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes

Target

  • Clone
  • Trastuzumab
  • Host
  • Human
  • Target Species
  • Human
  • Gene Name
  • Erb-b2 receptor tyrosine kinase 2 & Epidermal growth factor receptor
  • Synonyms
  • ERBB2 & EGFR; Erb-b2 receptor tyrosine kinase 2 & Epidermal growth factor receptor
  • Target II
  • EGFR
  • Clone
  • Human
  • Target Species
  • EGFR
  • Gene ID
  • 1956
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