Anti-Mesothelin (HN1) 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
Mesothelin

Targeting Cell Type
T cell

Targeting Diseases
Pancreatic cancer, Ovarian cancer, Lung cancer, Malignant pleural mesothelioma tumors (MPM tumors)

Generation
Third

Vector Name
pCDCAR1

Vector Length
~8kb

Vector Type
Retroviral

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 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.
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

Customize Your CAR Products

Published Data

CAR scFv data FCM

Fig.1 FACS analysis of HN1 on mesothelin-expressing cancer cells.

CAR Construction :

Fig.1 FACS analysis of HN1 on mesothelin-expressing cancer cells.

The HN1 bound to H9 cells, not A431 cells. HN1 also bound to OVCAR-8, NCI-H226 and YOU cells. H9: the transfected A431 cell line stably expressing mesothelin.

Ho, M., Feng, M., Fisher, R. J., Rader, C., & Pastan, I. (2011). A novel high‐affinity human monoclonal antibody to mesothelin. International Journal of Cancer, 128(9), 2020-2030.

Complete CAR data Funcs

Fig.2 Cytolytic activity of CAR-T cells.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.2 Cytolytic activity of CAR-T cells.

The cytolytic activity of CAR-T cells were analyzed on H226-MSLN-PDL1, PANC1-MSLNPDL1 and OVCAR3-MSLN-PDL1 luciferase positive target cells by bioluminescence assay at indicated Effector: Target (E:T) ratios.

Lal, S., Wang, G., Chen, Z., Xiang, X., Liang, C., & Huang, X. F. (2019). Co-expression of PD-L1 antibodies enhances the anti-tumor efficacy of chimeric antigen receptor T cells. Journal of Cancer Research and Immuno-oncology, 5, 119.

Complete CAR data Funcs

Fig.3 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.3 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

NSG mice were grouped and injected on their right flanks with 1E6 H226-MSLN-PDL1 luciferase cells. On day 3rd, the mice were treated with 5E6 indicated CAR-T cells. Tumor growth was quantified by BLI.

Complete CAR data Funcs

Fig.4 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.4 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

Tumor growth was quantified by BLI and calculated.

Complete CAR data Funcs

Fig.5 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.5 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

Kaplan-Meier survival curve showing the percent survival.

Complete CAR data Funcs

Fig.6 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.6 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

NSG mice were grouped and injected on their right flanks with 1E6 PANC1-MSLN-PDL1. On day 3rd, the mice were treated with 5E6 indicated CAR-T cells. Tumor growth was quantified by BLI.

Complete CAR data Funcs

Fig.7 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.7 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

Tumor growth was quantified by BLI and calculated.

Complete CAR data Funcs

Fig.8 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

CAR Construction : HN1 scfv-41BB-CD3ζ

Fig.8 Mesothelin targeted CAR-T cells enhances anti-tumor efficacy in xenograft mouse models.

Kaplan-Meier survival curve showing the percent survival.

More Published Data More Published Data

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.