Anti-HER2 (Trastuzumab) h(4-1BB-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
HER2

Targeting Cell Type
T cell

Targeting Diseases
Breast Carcinomas

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 antigen-nonspecific 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

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Published Data

Complete CAR data ELISA

Fig.1 Cytokine release assay.

CAR Construction : Trastuzumab-CD28-CD3ζ

Fig.1 Cytokine release assay.

HER2-CAR cells were incubated with 1 μg/ml HER2-Fc protein or cocultured with MDA-HER2 or JIMT-1 (HER2 positive) or MDA (HER2 negative) target cells in 1:1 T cell to tumor cell ratio.

Szöőr, Á., Tóth, G., Zsebik, B., Szabó, V., Eshhar, Z., Abken, H., & Vereb, G. (2020). Trastuzumab derived HER2-specific CARs for the treatment of trastuzumab-resistant breast cancer: CAR T cells penetrate and eradicate tumors that are not accessible to antibodies. Cancer Letters, 484, 1-8.

Complete CAR data BI

Fig.3 HER2-CAR T cells eliminate HER2 positive tumor xenografts in vivo.

CAR Construction : Trastuzumab-CD28-CD3ζ

Fig.3 HER2-CAR T cells eliminate HER2 positive tumor xenografts in vivo.

Representative images of MDA-HER2.ffLUC injected animals after CAR-T treatment.

Complete CAR data Cyt

Fig.4 Cytotoxicity assay

CAR Construction : Trastuzumab-CD28-CD3ζ

Fig.4 Cytotoxicity assay

XTT-based cytotoxicity assay using HER2 CAR T cells or non-modified mouse T cells and HER2 positive JIMT-1 cells as target at various (2.5:1-0.04:1) T cell to tumor cell ratios.

Tóth, G., Szöllősi, J., Abken, H., Vereb, G., & Szöőr, Á. (2020). A small number of HER2 redirected CAR T cells significantly improves immune response of adoptively transferred mouse lymphocytes against human breast cancer xenografts. International journal of molecular sciences, 21(3), 1039.

Complete CAR data FuncS

Fig.5 Antitumor activity of HER2-CAR mouse T cells in a xenograft model

CAR Construction : Trastuzumab-CD28-CD3ζ

Fig.5 Antitumor activity of HER2-CAR mouse T cells in a xenograft model

Quantitative measurement of tumor volumes and Kaplan-Meier survival curve.

Complete CAR data FCM & ELISA

Fig.6 Cytokine release assay.

CAR Construction : Trastuzumab-CD28-CD3ζ, Trastuzumab-4-1BB-CD3ζ

Fig.6 Cytokine release assay.

Quantification of CD107a degranulation and IFNγ production by HER2-CAR T.

Priceman, S. J., Tilakawardane, D., Jeang, B., Aguilar, B., Murad, J. P., Park, A. K., ... & Brown, C. E. (2018). Regional Delivery of Chimeric Antigen Receptor–Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the BrainIntraventricular HER2-CAR T Cells for Breast Cancer Brain Metastases. Clinical Cancer Research, 24(1), 95-105.

Complete CAR data FCM

Fig.7 Tumor killing assay.

CAR Construction : Trastuzumab-CD28-CD3ζ, Trastuzumab-4-1BB-CD3ζ

Fig.7 Tumor killing assay.

Tumor killing assay comparing HER2-28z and HER2-BBz CAR T cells following a 3-day coculture with the indicated tumor targets, assessed by flow cytometry.

Complete CAR data BI

Fig.8 Local intratumoral delivery of HER2- CAR T cells eradicates xenograft models of breast cancer brain metastasis.

CAR Construction : Trastuzumab-CD28-CD3ζ, Trastuzumab-4-1BB-CD3ζ

Fig.8 Local intratumoral delivery of HER2- CAR T cells eradicates xenograft models of breast cancer brain metastasis.

BBM1 tumor-bearing mice were treated 8 days after tumor injection with Mock, HER2-28z, or HER2-BBz CAR T cells (0.5 106 cells).

Complete CAR data FuncS

Fig.9 Treatment of a breast cancer xenograft by ErbB2-CAR-transduced PBLs.

CAR Construction : Trastuzumab-CD28-CD3ζ, Trastuzumab-CD28-4-1BB-CD3ζ

Fig.9 Treatment of a breast cancer xenograft by ErbB2-CAR-transduced PBLs.

Adoptively transferred (i.v.) 4D5-28Z or 4D5-CD8-28BBZ- or SP6-28Z-transduced PBLs were administered to animals bearing human breast tumor.

Zhao, Y., Wang, Q. J., Yang, S., Kochenderfer, J. N., Zheng, Z., Zhong, X., ... & Morgan, R. A. (2009). A herceptin-based chimeric antigen receptor with modified signaling domains leads to enhanced survival of transduced T lymphocytes and antitumor activity. The Journal of Immunology, 183(9), 5563-5574.

CAR scFv data SPR

Fig.10 SPR binding assay.

CAR Construction :

Fig.10 SPR binding assay.

SPR binding sensorgrams for the interaction of HER2 wild type immobilized DARP in trastuzumab.

Epa, V. C., Dolezal, O., Doughty, L., Xiao, X., Jost, C., Plückthun, A., & Adams, T. E. (2013). Structural model for the interaction of a designed Ankyrin Repeat Protein with the human epidermal growth factor receptor 2. PLoS One, 8(3), e59163.

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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.