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pSBCAR1 CD22 (HA22SH) h(28OXζ) (CAR-SB-02LX253)

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All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

Sleeping Beauty (SB) transposon, a type of nonviral integrative vectors, provides an alternative to modify primary T cells. Creative biolabs has developed SB transposon CAR vector pSBCAR1 CD22 (HA22SH) h(28OXζ), which is constructed for the engineering of T cells to target human CD22. The T cells are genetically modified through transduction with a nonviral vector expressing scFv of anti-CD22 antibody linked to a CD28 transmembrane domain/ endodomain and OX40, CD3-zeta signaling domains. And the vector product was designed for the treatment of Acute lymphoblastic leukemia (ALL).

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Details

  • Target
  • CD22
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Acute lymphoblastic leukemia (ALL)
  • Generation
  • Third
  • Vector Name
  • pSBCAR1
  • Vector Length
  • ~6kb
  • Vector Type
  • Sleeping Beauty (SB) transposon
  • Receptor Construction
  • scFv-CD28-OX40-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.
    OX40
    OX40, also known as CD134 or TNFRSF4 is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation. The interaction between OX40 and its binding partner, OX40L (CD252) plays an important role in antigen-specific T-cell expansion and survival. OX40 and OX40L also regulate cytokine production from T cells and modulate cytokine receptor signaling. OX40 cosignaling in CAR improve redirected T-cell effector functions and enhance anti-tumor activity.
    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
  • HA22SH
  • Host
  • Mouse
  • Target Species
  • Human
  • Gene Name
  • CD22
  • Synonyms
  • CD22;CD22; CD22 Molecule; CD22 Molecule; CD22 Antigen; Sialic Acid-Binding Ig-Like Lectin 2; B-Lymphocyte Cell Adhesion Molecule; T-Cell Surface Antigen Leu-14; SIGLEC-2;

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  • Published Data
Complete CAR data FuncS

Fig.1 Comparison of CD22-CAR and CD19-CAR-mediated lysis.

CAR Construction : HA22SH-CD28-CD3ζ Latest CAR Construction

Fig.1 Comparison of CD22-CAR and CD19-CAR-mediated lysis.

51Cr-release assay to evaluate lytic activity of CD22 HA22SH-28z second-generation CAR (inverted triangle), m971-28z second-generation CAR (gray triangle), CD19 CAR (squares), or mock transduced T cells (circles) against ALL lines.

Haso, W., Lee, D. W., Shah, N. N., Stetler-Stevenson, M., Yuan, C. M., Pastan, I. H., ... & Orentas, R. J. (2013). Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology, 121(7), 1165-1174.

Complete CAR data AM

Fig.2 Cytokine release by CAR-transduced T cells.

CAR Construction : HA22SH-CD28-CD3ζ, HA22SH-CD28-41BB-CD3ζ Latest CAR Construction

Fig.2 Cytokine release by CAR-transduced T cells.

CAR-transduced T cells (vectors listed, x-axis) were incubated with irradiated CD22-high (Raji, column 1), CD22-low (NALM6-GL, column 2), or CD22-negative (K562, column 3) leukemia cell lines at a ratio of 10:1 for 24 hours and culture supernatants analyzed for IFN-γ (top row), IL-2 (second row), and TNF-α (third row).

Haso, W., Lee, D. W., Shah, N. N., Stetler-Stevenson, M., Yuan, C. M., Pastan, I. H., ... & Orentas, R. J. (2013). Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology, 121(7), 1165-1174.

Complete CAR data BI

Fig.3 Evaluation of CD22 CARs in vivo.

CAR Construction : HA22SH-CD28-CD3ζ Latest CAR Construction

Fig.3 Evaluation of CD22 CARs in vivo.

On day 0, NSG mice were injected intravenously with 5 × 10^5 NALM6-GL cells. On day 3 mice received 1 × 10^7 CAR+ T cells (HA22SH-28z (n = 5) or m971-28z (n = 5) or mock T cells (n = 5). Bioluminescent imaging pre-treatment (day 3), day 7 and day 15 after intravenous injection of NALM6-GL.

Haso, W., Lee, D. W., Shah, N. N., Stetler-Stevenson, M., Yuan, C. M., Pastan, I. H., ... & Orentas, R. J. (2013). Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood, The Journal of the American Society of Hematology, 121(7), 1165-1174.

More Published Data More Published Data

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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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