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pCDCAR1 Lewis Y h(BBζ) (CAR-ZP8397)


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

The vector of anti-Lewis Y chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human Lewis Y. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-Lewis Y antibody linked to 4-1BB and CD3ζ signaling domains. And the vector product was designed for the treatment of gastric cancer.

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Details

  • Target
  • Lewis Y
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • gastric cancer
  • Generation
  • Second
  • Vector Name
  • pCDCAR1
  • Vector Length
  • ~8kb
  • Vector Type
  • Lentiviral vector
  • Receptor Construction
  • scFv-4-1BB-CD3ζ
  • Discription of Signaling Cassetes
  • 41BB
    CD137 (also known as 4-1BB) is a surface co-stimulatory glycoprotein originally described as present on activated T lymphocytes, which belongs to the tumor necrosis factor (TNF) receptor superfamily. It is expressed mainly on activated CD4+ and CD8+ T cells, and binds to a high-affinity ligand (4-1BBL) expressed on several antigen-presenting cells such as macrophages and activated B cells. On the basis of preclinical observation, this molecule can promote the persistence of antigen-specific and antigennonspecific chimeric antigen receptor T-cells to significantly increases antitumor 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
  • MB311
  • Host
  • Humanized
  • Target Species
  • Human
  • Gene Name
  • Lewis Y
  • Synonyms
  • Lewis Y

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  • Published Data
CAR scFv data FCM

Fig.3 Histogram of flow cytometry based binding of MB311 and MB314 to purified Natural Killer (NK) cells.

CAR Construction : Latest CAR Construction

Fig.3 Histogram of flow cytometry based binding of MB311 and MB314 to purified Natural Killer (NK) cells.

A human (Fab)'2 fragment was used as control. For detection a phycoerythrin (PE)-labeled anti-human F(ab') fragment was used

Roucka, M., Zimmermann, K., Fido, M., & Nechansky, A. (2016). Application of lectin array technology for biobetter characterization: Its correlation with FcγRIII binding and ADCC. Microarrays, 6(1), 1.

CAR scFv data FCM

Fig.1 Binding of MB311 to the Lewis-Y positive tumor cell line SKBR-3 was determined by flow cytometry.

CAR Construction : Latest CAR Construction

Fig.1 Binding of MB311 to the Lewis-Y positive tumor cell line SKBR-3 was determined by flow cytometry.

Geometric Mean fluorescence intensity (MFI) was plotted vs. the logarithm of the antibody concentration and fitted using a sigmoidal four parameter fit using GraphPad Prism 4 software for calculation of EC 50 values.

Kircheis, R., Halanek, N., Koller, I., Jost, W., Schuster, M., Gorr, G., ... & Nechansky, A. (2012, July). Correlation of ADCC activity with cytokine release induced by the stably expressed, glyco-engineered humanized Lewis Y-specific monoclonal antibody MB314. In MAbs (Vol. 4, No. 4, pp. 532-541). Taylor & Francis.

CAR scFv data FCM

Fig.2 SKBR-3 target cells and effector cells (PBMCs from a healthy volunteer donor) at an E:T ratio of 25:1 were incubated with 74 ng/ml of MB311 for FACS analysis.

CAR Construction : Latest CAR Construction

Fig.2 SKBR-3 target cells and effector cells (PBMCs from a healthy volunteer donor) at an E:T ratio of 25:1 were incubated with 74 ng/ml of MB311 for FACS analysis.

Intracellular Expression of tumor necrosis factor (TNF) by CD14+ cells, but not by CD3+ or CD56+ cells. SKBR-3 target cells and effector cells.

Kircheis, R., Halanek, N., Koller, I., Jost, W., Schuster, M., Gorr, G., ... & Nechansky, A. (2012, July). Correlation of ADCC activity with cytokine release induced by the stably expressed, glyco-engineered humanized Lewis Y-specific monoclonal antibody MB314. In MAbs (Vol. 4, No. 4, pp. 532-541). Taylor & Francis.

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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