Anti-PD-L1 (Atezolizumab) 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
PD-L1

Targeting Cell Type
T cell

Targeting Diseases
NSCLC, Melanoma, Breast Cancer, Glioma, Lymphoma, Leukemia and Various Urinary Tract Tumors, Gastrointestinal Tumors, Reproductive System Tumors

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

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Published Data

Complete CAR data FCM

Fig.1 Expansion of PD-L1-CAR and CD19-CAR T cells in vitro for 14 days.

CAR Construction : Atezolizumab scFv-BBζ

Fig.1 Expansion of PD-L1-CAR and CD19-CAR T cells in vitro for 14 days.

Data represented technical triplicates using T cells from one donor and were displayed as mean ± SEM.

Liu, M., Wang, X., Li, W., Yu, X., Flores-Villanueva, P., Xu-Monette, Z. Y., ... & Li, Y. (2020). Targeting PD-L1 in non-small cell lung cancer using CAR T cells. Oncogenesis, 9(8), 1-11.

Complete CAR data Cyt

Fig.2 Cytotoxic activity of PD-L1-CAR T cells after 4 and 20 h of co-culture with human NSCLC cell lines.

CAR Construction : Atezolizumab scFv-BBζ

Fig.2 Cytotoxic activity of PD-L1-CAR T cells after 4 and 20 h of co-culture with human NSCLC cell lines.

PD-L1-CAR T cells and CD19-CAR T cells were used as effector cells at various ratios of effector (E): target (T).

Liu, M., Wang, X., Li, W., Yu, X., Flores-Villanueva, P., Xu-Monette, Z. Y., ... & Li, Y. (2020). Targeting PD-L1 in non-small cell lung cancer using CAR T cells. Oncogenesis, 9(8), 1-11.

Complete CAR data FCM

Fig.3 Flow cytometry histogram of the surface antigen expression of PD-L1 in human NSCLC cell line.

CAR Construction : Atezolizumab scFv-BBζ

Fig.3 Flow cytometry histogram of the surface antigen expression of PD-L1 in human NSCLC cell line.

Data represented technical triplicates using T cells from one donor and were shown as mean ± SEM.

Liu, M., Wang, X., Li, W., Yu, X., Flores-Villanueva, P., Xu-Monette, Z. Y., ... & Li, Y. (2020). Targeting PD-L1 in non-small cell lung cancer using CAR T cells. Oncogenesis, 9(8), 1-11.

Complete CAR data BI

Fig.4 Serial bioluminescence imaging of tumor progression and regression in each group (n = 3 mice per group).

CAR Construction : Atezolizumab scFv-BBζ

Fig.4 Serial bioluminescence imaging of tumor progression and regression in each group (n = 3 mice per group).

Experimental design of tumor cell xenograft model treated with CAR T cells and/or irradiation.

Liu, M., Wang, X., Li, W., Yu, X., Flores-Villanueva, P., Xu-Monette, Z. Y., ... & Li, Y. (2020). Targeting PD-L1 in non-small cell lung cancer using CAR T cells. Oncogenesis, 9(8), 1-11.

Complete CAR data IHC

Fig.5 Representative images of CD3 IHC in PD-L1-CAR T cell-treated and irradiation-treated NSCLC tumors.

CAR Construction : Atezolizumab scFv-BBζ

Fig.5 Representative images of CD3 IHC in PD-L1-CAR T cell-treated and irradiation-treated NSCLC tumors.

Scale bars, 100 µm.

Liu, M., Wang, X., Li, W., Yu, X., Flores-Villanueva, P., Xu-Monette, Z. Y., ... & Li, Y. (2020). Targeting PD-L1 in non-small cell lung cancer using CAR T cells. Oncogenesis, 9(8), 1-11.

CAR scFv data FCM

Fig.1 The surface expression of PD-L1 was determined at 24 h post treatment by flow cytometry.

CAR Construction :

Fig.1 The surface expression of PD-L1 was determined at 24 h post treatment by flow cytometry.

Effect of atezolizumab on PD-L1 expression in MDA-MB-231 cells.

Saleh, R., Taha, R. Z., Sasidharan Nair, V., Alajez, N. M., & Elkord, E. (2019). PD-L1 blockade by atezolizumab downregulates signaling pathways associated with tumor growth, metastasis, and hypoxia in human triple negative breast cancer. Cancers, 11(8), 1050.

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