Anti-NY-ESO-1 (3E4M5) h(CD28-CD3ζ) CAR, pCDCAR1 vector

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

Details

Target
NY-ESO-1

Targeting Cell Type
T cell

Targeting Diseases
Neuroblastoma, Synovial Sarcoma, Malignant Melanoma, Ovarian Cancer, Colorectal Cancer, Liver Cancer, Urinary Tract Skin Cancer, Multiple Myeloma, Lung Cancer.

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 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 cell 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

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Published Data

Complete CAR data FCM

Fig.1 The A2/NY-ESO-1157-specific CAR was transduced into peripheral blood T cells.

CAR Construction : 3E4M5 scFv-28ζ

Fig.1 The A2/NY-ESO-1157-specific CAR was transduced into peripheral blood T cells.

These CAR-T cells were stained with 5 μg/mL A2/NY-ESO-1157 tetramer or A2/HIV Gag77 tetramer.

Maruta, M., Ochi, T., Tanimoto, K., Asai, H., Saitou, T., Fujiwara, H., ... & Yasukawa, M. (2019). Direct comparison of target-reactivity and cross-reactivity induced by CAR-and BiTE-redirected T cells for the development of antibody-based T-cell therapy. Scientific reports, 9(1), 1-13.

Complete CAR data FCM

Fig.2 A2/NY-ESO-1157-specific BiTE engages peripheral blood T cells with target cells.

CAR Construction : 3E4M5 scFv-28ζ

Fig.2 A2/NY-ESO-1157-specific BiTE engages peripheral blood T cells with target cells.

Dotted lines show the isotype control.

Complete CAR data FuncS

Fig.3 A2/NY-ESO-1157 CAR- and BiTE-redirected T cells kill HLA-A2+NY-ESO-1+ target cells in vitro.

CAR Construction : 3E4M5 scFv-28ζ

Fig.3 A2/NY-ESO-1157 CAR- and BiTE-redirected T cells kill HLA-A2+NY-ESO-1+ target cells in vitro.

All the experiments were performed in triplicate and error bars depict the SD.

Complete CAR data FuncS

Fig.4 A2/NY-ESO-1157 CAR- and BiTE-redirected T cells show sufcient functional avidity to induce anti-myeloma reactivity in vivo.

CAR Construction : 3E4M5 scFv-28ζ

Fig.4 A2/NY-ESO-1157 CAR- and BiTE-redirected T cells show sufcient functional avidity to induce anti-myeloma reactivity in vivo.

Two million U266/SLR cells were intravenously injected into NOG mice.

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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.