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pCDCAR1 GPC3 h(BBζ) (CAR-ZP7397)


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

The vector of anti-GPC3 chimeric antigen receptor (CAR) is constructed for the engineering of T cells to target Human GPC3. The T cells are genetically modified through transduction with a lentiviral vector expressing scFv of anti-GPC3 antibody linked to 4-1BB and CD3ζ signaling domains. And the vector product was designed for the treatment of hepatocellular carcinoma.

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Details

  • Target
  • GPC3
  • Targeting Cell Type
  • T cell
  • Targeting Diseases
  • hepatocellular carcinoma
  • 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 antigennonspecific 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

  • Clone
  • Y035
  • Host
  • Humanized
  • Target Species
  • Human
  • Gene Name
  • glypican 3
  • Synonyms
  • GPC3;GPC3; glypican 3; SGB; DGSX; MXR7; SDYS; SGBS; OCI-5; SGBS1; GTR2-2;

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  • Published Data
Complete CAR data FCM

Fig.1 Subset composition of Y035 CAR-GPC3 T-cell products infused in all patients.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.1 Subset composition of Y035 CAR-GPC3 T-cell products infused in all patients.

Y035 CAR-GPC3 T cells, which were successfully generated for HCC patients and Characteristics of subset composition.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.2 Characteristics of Y035 CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.2 Characteristics of Y035 CAR-GPC3 T cells.

Representative histograms and dot plots of infused Y035 CAR-GPC3 T-cell products (patients P6 and P10). CM, central memory; EM, effector memory; TEMRA, terminally differentiated effector memory T cells.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.3 Persistence of CAR-GPC3 T cells as determined by cytokine levels in the patients with HCC.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.3 Persistence of CAR-GPC3 T cells as determined by cytokine levels in the patients with HCC.

Results of cytokine analyses in P3 after Y035 CAR-GPC3 T cells infusion.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.4 Persistence of CAR-GPC3 T cells as determined by cytokine levels in the patients with HCC.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.4 Persistence of CAR-GPC3 T cells as determined by cytokine levels in the patients with HCC.

Results of cytokine analyses in P12 after Y035 CAR-GPC3 T cells infusion.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.5 Persistence of CAR-GPC3 T cells as determined by cytokine levels in the patients with HCC.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.5 Persistence of CAR-GPC3 T cells as determined by cytokine levels in the patients with HCC.

Results of cytokine analyses in P13 after Y035 CAR-GPC3 T cells infusion.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.6 Clinical responses and exploratory subgroup analysis in patients with HCC administered CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.6 Clinical responses and exploratory subgroup analysis in patients with HCC administered CAR-GPC3 T cells.

Swimmer's plot of the time after CAR-T for each patient. A total of 13 patients with HCC received CAR-GPC3 T-cell infusions. Eligibility criteria included an expected survival duration of 12 weeks.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.7 Clinical responses and exploratory subgroup analysis in patients with HCC administered CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.7 Clinical responses and exploratory subgroup analysis in patients with HCC administered CAR-GPC3 T cells.

Kaplan-Meier curve of OS for patients. Censored patients (those alive or lost to follow-up at the time of data analysis) are indicated by plus signs.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.8 Tumor responses in two patients with advanced HCC (P3 and P13) administered CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.8 Tumor responses in two patients with advanced HCC (P3 and P13) administered CAR-GPC3 T cells.

CT scans of one target lesion (yellow arrow) in the liver of P3 taken before and after CAR-GPC3 T-cell infusion.

Shi, D., Shi, Y., Kaseb, A. O., Qi, X., Zhang, Y., Chi, J., ... & Zhai, B. (2020). Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I TrialsPhase I Trials of CAR-GPC3 T Cells for Advanced HCC. Clinical Cancer Research, 26(15), 3979-3989.

Complete CAR data Funcs

Fig.9 CAR-GPC3 expansion in peripheral blood of patients administered with CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.9 CAR-GPC3 expansion in peripheral blood of patients administered with CAR-GPC3 T cells.

GPC3 CAR copies in peripheral blood rapidly increased to their peak at within one week post-infusion and then decreased gradually on each cycle.

Sun, H., Xing, C., Jiang, S., Yu, K., Dai, S., Kong, H., ... & Shi, K. (2022). Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Frontiers in immunology, 13.

Complete CAR data Funcs

Fig.10 TNF-a secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.10 TNF-a secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

Cytokine tumor necrosis factor-126 α (TNF-α) were elevated and reached their peaks at 3 days after each cycle of CAR T-cell 127 infusion, and then dropped to normal level after about 2 weeks.

Sun, H., Xing, C., Jiang, S., Yu, K., Dai, S., Kong, H., ... & Shi, K. (2022). Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Frontiers in immunology, 13.

Complete CAR data Funcs

Fig.11 IFN-γ secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.11 IFN-γ secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

Cytokine interferon-γ (IFN-γ) were elevated and reached their peaks at 3 days after each cycle of CAR T-cell 127 infusion, and then dropped to normal level after about 2 weeks.

Sun, H., Xing, C., Jiang, S., Yu, K., Dai, S., Kong, H., ... & Shi, K. (2022). Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Frontiers in immunology, 13.

Complete CAR data Funcs

Fig.12 IL-6 secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.12 IL-6 secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

Cytokine interleukin-6 (IL-6) were elevated and reached their peaks at 3 days after each cycle of CAR T-cell 127 infusion, and then dropped to normal level after about 2 weeks.

Sun, H., Xing, C., Jiang, S., Yu, K., Dai, S., Kong, H., ... & Shi, K. (2022). Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Frontiers in immunology, 13.

Complete CAR data Funcs

Fig.13 IL-10 secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.13 IL-10 secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

cytokine interleukin-10 (IL-10) were elevated and reached their peaks at 3 days after each cycle of CAR T-cell 127 infusion, and then dropped to normal level after about 2 weeks.

Sun, H., Xing, C., Jiang, S., Yu, K., Dai, S., Kong, H., ... & Shi, K. (2022). Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Frontiers in immunology, 13.

Complete CAR data Funcs

Fig.14 IL-15 secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

CAR Construction : Y035 scfv-CD28-CD3ζ Latest CAR Construction

Fig.14 IL-15 secretion in peripheral blood of patients administered with CAR-GPC3 T cells.

Cytokine interleukin-15 (IL-15) were elevated and reached their peaks at 3 days after each cycle of CAR T-cell 127 infusion, and then dropped to normal level after about 2 weeks.

Sun, H., Xing, C., Jiang, S., Yu, K., Dai, S., Kong, H., ... & Shi, K. (2022). Long term complete response of advanced hepatocellular carcinoma to glypican-3 specific chimeric antigen receptor T-Cells plus sorafenib, a case report. Frontiers in immunology, 13.

More Published Data More Published Data

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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.

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