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pCDCAR1 EGFR h(28ζ) (CAR-ZP8034)

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

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Details

  • Target
  • EGFR
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Melanoma
  • 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
  • MAb528
  • 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 Cell-surface EGFRs were measured by FACS with flow cytometry. The cells were collected for FACS analysis of the distribution of FITC-positive cells.

CAR Construction : Latest CAR Construction

Fig.1 Cell-surface EGFRs were measured by FACS with flow cytometry. The cells were collected for FACS analysis of the distribution of FITC-positive cells.

Decreased levels of total and cell-surface EGFR in DiFi5 cells relative to parental DiFi cells.

Lu, Y., Li, X., Liang, K., Luwor, R., Siddik, Z. H., Mills, G. B., ... & Fan, Z. (2007). Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab. Cancer research, 67(17), 8240-8247.
CAR scFv data FCM

Fig.2 Flow cytometric analysis of BaF/3.

CAR Construction : Latest CAR Construction

Fig.2 Flow cytometric analysis of BaF/3.

Data are representative of binding observed in all samples.

Perera, R. M., Zoncu, R., Johns, T. G., Pypaert, M., Lee, F. T., Mellman, I., ... & Scott, A. M. (2007). Internalization, intracellular trafficking, biodistribution of monoclonal antibody 806: a novel anti-epidermal growth factor receptor antibody. Neoplasia, 9(12), 1099-1110.
CAR scFv data FCM

Fig.3 Differential sensitivity of EGFRvIII monoclonal antibodies DH8.3/Ab-18 and 4-5H by FACS analysis.

CAR Construction : Latest CAR Construction

Fig.3 Differential sensitivity of EGFRvIII monoclonal antibodies DH8.3/Ab-18 and 4-5H by FACS analysis.

All mAbs recognized EGFRvIII on the cell surface, mAb 528 recognized both wild-type EGFR and EGFRvIII, whereas mAbs 4-5H and DH8.3/Ab-18 recognized EGFRvIII only.

Yu, H., Gong, X., Luo, X., Han, W., Hong, G., Singh, B., & Tang, C. K. (2008). Co-expression of EGFRvIII with ErbB-2 enhances tumorigenesis: EGFRvIII mediated constitutively activated and sustained signaling pathways, whereas EGF-induced a transient effect on EGFR-mediated signaling pathways. Cancer Biology & Therapy, 7(11), 1818-1828.

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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