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pCDCAR1 HER2 h(iMC; iRC9) (CAR-ZP6899)


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

The vector of anti-HER2 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human HER2. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-HER2 antibody linked to MyD88-CD40-FKBP and FKBP12-caspase-9 signaling domains. And the vector product was designed for the treatment of breast cancer.

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Details

  • Target
  • HER2
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • Breast cancer
  • Vector Name
  • pCDCAR1
  • Vector Length
  • ~8kb
  • Vector Type
  • Lentiviral vector
  • Receptor Construction
  • Dual-Switch CAR(HER2 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9)
  • Discription of Signaling Cassetes
  • 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
  • 4D5-8
  • Host
  • Mouse
  • Target Species
  • Human
  • Gene Name
  • erb-b2 receptor tyrosine kinase 2
  • Synonyms
  • NEU; NGL; HER2; TKR1; CD340; HER-2; MLN 19; HER-2/neu

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  • Published Data
Complete CAR data ELISA

Fig.1 Cytokine release assay.

CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Latest CAR Construction

Fig.1 Cytokine release assay.

To assess antitumour activity in vitro, T cells (co-labeled with GFP) were co-cultured at various E:T ratios with the pancreatic tumour target cell line HPAC-RFP ± Rim. Two days post-seeding, culture supernatants from a duplicate plate were analyzed for IL-2 production by ELISA.

Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137.

Complete CAR data BI

Fig.2 Activation of the iMC switch enhances HER2 DS CAR-T cell proliferation in vitro.

CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Latest CAR Construction

Fig.2 Activation of the iMC switch enhances HER2 DS CAR-T cell proliferation in vitro.

The co-culture containing HPAC-RFP and iRC9 or HER2 DS CAR-T cells-GFP on day 7 in the presence or absence of Rim.

Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137.

Complete CAR data BI

Fig.3 Tumor killing assay in vivo.

CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Latest CAR Construction

Fig.3 Tumor killing assay in vivo.

iMC activation enhances HER2+ tumor killing.

Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137.

Complete CAR data BI

Fig.4 CAR-T proliferation assay in vivo.

CAR Construction : 4D5-8 scFv-MyD88-CD40-FKBP-CD3ζ; ∆CD19-FKBP12-caspase-9 Latest CAR Construction

Fig.4 CAR-T proliferation assay in vivo.

iMC activation enhances HER2 DS CAR-T cell proliferation.

Duong, M. T., Collinson-Pautz, M. R., Morschl, E., Lu, A., Szymanski, S. P., Zhang, M., ... & Bayle, J. H. (2019). Two-dimensional regulation of CAR-T cell therapy with orthogonal switches. Molecular Therapy-Oncolytics, 12, 124-137.

CAR scFv data ELISA

Fig.5 Comparison of measured affinities of 4D5 mutated antibodies.

CAR Construction : Latest CAR Construction

Fig.5 Comparison of measured affinities of 4D5 mutated antibodies.

p185HER2ECD binding affinity of mAb 4D5 variants.

Carter, P., Presta, L. E. N., Gorman, C. M., Ridgway, J. B., Henner, D., Wong, W. L., ... & Shepard, H. M. (1992). Humanization of an anti-p185HER2 antibody for human cancer therapy. Proceedings of the National Academy of Sciences, 89(10), 4285-4289.

More Published Data More Published Data

Customer Reviews and Q&As

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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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