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pCDCAR1 SLAMF7 h(28ζ) (CAR-ZP7340)


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

The vector of anti-SLAMF7 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human SLAMF7. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-SLAMF7 antibody linked to CD28 and CD3ζ signaling domains. And the vector product was designed for the treatment of Lung malignancy.

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Details

  • Target
  • SLAMF7
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Lung malignancy
  • 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 costimulatory 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.

Target

  • Clone
  • Elotuzumab
  • Host
  • Mouse
  • Target Species
  • Human
  • Gene Name
  • SLAM family member 7
  • Synonyms
  • 19A; CS1; CD319; CRACC

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  • Published Data
Complete CAR data FCM

Fig.1 Quantification of CD107a degranulation.

CAR Construction : Elotuzumab-CD28-CD3ζ Latest CAR Construction

Fig.1 Quantification of CD107a degranulation.

CD4+T cells and CD8+ T cells were assessed for SLAMF7-specific CD107a upregulation.

Amatya, C., Pegues, M. A., Lam, N., Vanasse, D., Geldres, C., Choi, S., ... & Kochenderfer, J. N. (2021). Development of CAR T cells expressing a suicide gene plus a chimeric antigen receptor targeting signaling lymphocytic-activation molecule F7. Molecular Therapy, 29(2), 702-717.

Complete CAR data ELISA

Fig.2 Determination of IFN-γ release.

CAR Construction : Elotuzumab-CD28-CD3ζ Latest CAR Construction

Fig.2 Determination of IFN-γ release.

Luc63-CD828Z or Luc90-CD828Z or untransduced T cells were cultured overnight with target cells. After the overnight culture, supernatant was assayed by ELISA for IFN-γ.

Amatya, C., Pegues, M. A., Lam, N., Vanasse, D., Geldres, C., Choi, S., ... & Kochenderfer, J. N. (2021). Development of CAR T cells expressing a suicide gene plus a chimeric antigen receptor targeting signaling lymphocytic-activation molecule F7. Molecular Therapy, 29(2), 702-717.

Complete CAR data ELISA

Fig.3 Determination of cytokines release.

CAR Construction : Elotuzumab-CD28-CD3ζ Latest CAR Construction

Fig.3 Determination of cytokines release.

Secretion of IFN-γ and IL-2 analyzed by enzyme-linked immunosorbent assay in supernatants obtained after a 20-hour coculture of effector and target cells.

Gogishvili, T., Danhof, S., Prommersberger, S., Rydzek, J., Schreder, M., Brede, C., ... & Hudecek, M. (2017). SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes. Blood, The Journal of the American Society of Hematology, 130(26), 2838-2847.

Complete CAR data Cyt

Fig.4 In vitro cytotoxicity of CAR cells.

CAR Construction : Elotuzumab-CD28-CD3ζ Latest CAR Construction

Fig.4 In vitro cytotoxicity of CAR cells.

Cytotoxic/cytolytic activity of CD4+ and CD8+ SLAMF7-CAR T cells within 4 and 20 hours of coculture, respectively, with myeloma cell lines.

Gogishvili, T., Danhof, S., Prommersberger, S., Rydzek, J., Schreder, M., Brede, C., ... & Hudecek, M. (2017). SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes. Blood, The Journal of the American Society of Hematology, 130(26), 2838-2847.

Complete CAR data BI

Fig.5 Anti-tumor Activity of CAR-T cells.

CAR Construction : Elotuzumab-CD28-CD3ζ Latest CAR Construction

Fig.5 Anti-tumor Activity of CAR-T cells.

NSG mice were inoculated with CD38+CD138+SLAMF7+ ffluc_eGFP-transduced MM.1S myeloma cells (IV) and, 14 days later, treated with a single dose of SLAMF7-CAR T cells or CD19-CAR (control) T cells.

Gogishvili, T., Danhof, S., Prommersberger, S., Rydzek, J., Schreder, M., Brede, C., ... & Hudecek, M. (2017). SLAMF7-CAR T cells eliminate myeloma and confer selective fratricide of SLAMF7+ normal lymphocytes. Blood, The Journal of the American Society of Hematology, 130(26), 2838-2847.

Complete CAR data Cyt

Fig.6 In vitro cytotoxicity of CAR cells.

CAR Construction : Elotuzumab-CD28-41BB-CD3ζ Latest CAR Construction

Fig.6 In vitro cytotoxicity of CAR cells.

Chromium release killing assays comparing Luc90-CAR-T and HuLuc63 CAR-T. MM.1S-CG cells were used as target cells.

O’Neal, J., Ritchey, J. K., Cooper, M. L., Niswonger, J., Sofía González, L., Street, E., ... & DiPersio, J. F. (2022). CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+ CS1 expressing CAR-T cells. Leukemia, 36(6), 1625-1634.

Complete CAR data FuncS

Fig.7 Kaplan–Meier survival analysis.

CAR Construction : Elotuzumab-CD28-41BB-CD3ζ Latest CAR Construction

Fig.7 Kaplan–Meier survival analysis.

Mice were treated Kaplan Meier analysis= comparing survival of mice treated with 2X106 Luc90-CAR-T, HuLuc63-CAR-T or controls in MM.1S-CG mouse model .

O’Neal, J., Ritchey, J. K., Cooper, M. L., Niswonger, J., Sofía González, L., Street, E., ... & DiPersio, J. F. (2022). CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+ CS1 expressing CAR-T cells. Leukemia, 36(6), 1625-1634.

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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