Anti-PSCA (hu1G8) h(CD28-41BB-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
PSCA

Targeting Cell Type
T Cell

Targeting Diseases
Prostate Cancer

Generation
Third

Vector Name
pCDCAR1

Vector Length
~8kb

Vector Type
Lentiviral vector

Receptor Construction
scFv-CD28-41BB-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.

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 CD4-zeta to transmit a proliferative/survival signal, or all three can be used together.

Target

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Published Data

CAR scFv data FCM

Fig.1 After treatment with PBS or 1G8 (20 Ag/mL) for 24 hours, cells were stained with Annexin V and PI and analyzed by FACS.

CAR Construction :

Fig.1 After treatment with PBS or 1G8 (20 Ag/mL) for 24 hours, cells were stained with Annexin V and PI and analyzed by FACS.

1G8 induces cell death.

Gu, Z., Yamashiro, J., Kono, E., & Reiter, R. E. (2005). Anti–prostate stem cell antigen monoclonal antibody 1G8 induces cell death in vitro and inhibits tumor growth in vivo via a Fc-independent mechanism. Cancer research, 65(20), 9495-9500.

Complete CAR data FCM

Fig.2 Generation of anti-prostate stem cell antigen (PSCA) CAR-T cells.

CAR Construction : 1G8 scFv-28ζ

Fig.2 Generation of anti-prostate stem cell antigen (PSCA) CAR-T cells.

Representative flow cytometric analyses of transfected T cells detected by flow cytometry.

Wu, D., Lv, J., Zhao, R., Wu, Z., Zheng, D., Shi, J., ... & Yao, Y. (2020). PSCA is a target of chimeric antigen receptor T cells in gastric cancer. Biomarker Research, 8(1), 1-11.

Complete CAR data Cyt

Fig.3 Anti-PSCA CAR-T cells exhibited dramatic antitumor efficacy ex vivo.

CAR Construction : 1G8 scFv-28ζ

Fig.3 Anti-PSCA CAR-T cells exhibited dramatic antitumor efficacy ex vivo.

The lytic capacity towards MKN-28 cells, was analyzed at the indicated effector-to-target ratios in a 24 h lysis assay.

Wu, D., Lv, J., Zhao, R., Wu, Z., Zheng, D., Shi, J., ... & Yao, Y. (2020). PSCA is a target of chimeric antigen receptor T cells in gastric cancer. Biomarker Research, 8(1), 1-11.

Complete CAR data FuncS

Fig.4 Anti-PSCA CAR-T cells efficiently reduced tumor progression in BGC-823 models.

CAR Construction : 1G8 scFv-28ζ

Fig.4 Anti-PSCA CAR-T cells efficiently reduced tumor progression in BGC-823 models.

Percentage of T cells in the spleen of the BGC-823 models and representative FACS plots of the i.v group and the p.t group, respectively.

Wu, D., Lv, J., Zhao, R., Wu, Z., Zheng, D., Shi, J., ... & Yao, Y. (2020). PSCA is a target of chimeric antigen receptor T cells in gastric cancer. Biomarker Research, 8(1), 1-11.

Complete CAR data Inhibit

Fig.5 Anti-PSCA CAR-T cells suppressed tumor progression in MKN-28 model.

CAR Construction : 1G8 scFv-28ζ

Fig.5 Anti-PSCA CAR-T cells suppressed tumor progression in MKN-28 model.

Schematic representation depicting the time course of the experiment.

Wu, D., Lv, J., Zhao, R., Wu, Z., Zheng, D., Shi, J., ... & Yao, Y. (2020). PSCA is a target of chimeric antigen receptor T cells in gastric cancer. Biomarker Research, 8(1), 1-11.

More Published Data More Published Data

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