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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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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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CAR Construction : Y035 scfv-CD28-CD3ζ
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. |
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