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pCDCAR1 EGFRvIII h(28ζ) (CAR-MZ067)

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

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

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Details

  • Target
  • EGFRvIII
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Human glioblastoma (GBM)
  • Generation
  • Second
  • Vector Name
  • pCDCAR1
  • Vector Length
  • ~8kb
  • Vector Type
  • Lentiviral
  • 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-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.

Target

  • Clone
  • 3C10
  • Host
  • Mouse
  • Target Species
  • Human
  • Gene Name
  • Epidermal Growth Factor Receptor
  • Synonyms
  • EGFR;EGFR; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor; Receptor Tyrosine-Protein Kinase ErbB-1; Erb-B2 Receptor Tyrosine Kinase 1; Proto-Oncogene C-ErbB-1; EC 2.7.10.1; ERBB1; ERBB; HER1; Epidermal Growth Factor Receptor (Avian Erythroblastic Leukemia Viral (V-Erb-B) Oncogene Homolog); Erythroblastic Leukemia Viral (V-Erb-B) Oncogene Homolog (Avian);

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  • Published Data
CAR scFv data FCM

Fig.1 NIH-3T3 cells were transduced with a retroviral vector expressing EGFRvIII and a neomycin resistance gene.

CAR Construction : Latest CAR Construction

Fig.1 NIH-3T3 cells were transduced with a retroviral vector expressing EGFRvIII and a neomycin resistance gene.

Following selection in neomycin analogue G418, cells were subject to FACS analysis with anti-EGFRvIII mAb as shown.

Morgan, R. A., Johnson, L. A., Davis, J. L., Zheng, Z., Woolard, K. D., Reap, E. A., ... & Rosenberg, S. A. (2012). Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Human gene therapy, 23(10), 1043-1053.
Complete CAR data FCM

Fig.2 Development of CARs targeting EGFRvIII.

CAR Construction : 3C10 scFv-28ζ Latest CAR Construction

Fig.2 Development of CARs targeting EGFRvIII.

scFv genes were synthesized and fused to T-cell signaling domains from CD28 and CD3f followed by insertion into c-retroviral vector MSGV1 (diagram).

Morgan, R. A., Johnson, L. A., Davis, J. L., Zheng, Z., Woolard, K. D., Reap, E. A., ... & Rosenberg, S. A. (2012). Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Human gene therapy, 23(10), 1043-1053.
Complete CAR data FuncS

Fig.3 Anti-EGFRvIII CAR vector-engineered T cells specifically recognize EGFRvIII-expressing cells.

CAR Construction : 3C10 scFv-28ζ Latest CAR Construction

Fig.3 Anti-EGFRvIII CAR vector-engineered T cells specifically recognize EGFRvIII-expressing cells.

c-Retroviral vectors expressing the anti-EGFRvIII CARs (from murine mAbs 3C10 and L8A4 and human mAb 139) were used to transduced human T cells.

Morgan, R. A., Johnson, L. A., Davis, J. L., Zheng, Z., Woolard, K. D., Reap, E. A., ... & Rosenberg, S. A. (2012). Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma. Human gene therapy, 23(10), 1043-1053.

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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