
LINK . SPRINGER . COM {
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Title:
Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma | Molecular Cancer
Description:
Background This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. Methods A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. Results 4SCAR-T cells expanded for 1ā3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. Conclusion Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. Trial registration ClinicalTrials.gov Identifier: NCT03170141 . Registered 30 May 2017.
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Keywords {š}
cells, scart, patients, infusion, cell, gdspecific, cart, article, gbm, tumor, google, scholar, patient, cancer, antigen, study, fig, therapy, clinical, cas, blood, shenzhen, disease, peripheral, months, specific, table, number, intravenous, immune, car, size, glioblastoma, liu, microenvironment, response, progressive, expression, receptor, weeks, human, performed, university, data, safety, full, intracavitary, trial, treatment, mri,
Topics {āļø}
fourth-generation safety-designed car kenneth king-yip cheng tao chenĀ &Ā dinglan wu car-t-related adverse events chimeric antigen receptor interleukin-15āderived dendritic cells triple-negative breast cancer effectively distinguish pseudo-progression nhp/tyf lentivector system real-time quantitative pcr articleĀ google scholar article download pdf autologous gd2-specific 4scar 4scar-gd2 lentiviral vector infusing gd2-specific 4scar gd2-specific 4scar vectors post-gd2 specific 4scar packaging 4scar-gd2 vector immune-compromised leukemic patient exert tumor-killing functions received gd2-specific 4scar induces adaptive resistance received gd2-specific car post-infusion tumor specimens reporter gene imaging full access infused gd2-specific 4scar fewer cd163ā+ām2 macrophages gbm specimens post-infusion cells exert anti-glioblastoma jie mao anti-gd2 antibody treatment lung-ji chang specific antigen loss anti-cd47 antibodies treatment car t-cell therapy refractory b-cell lymphomas ganglioside gd2 enhances gd2 antigen loss privacy choices/manage cookies il-13ra2-specific car multiplex immunofluorescence staining clinical research committee pre-infusion tumor specimens wen lv small sample size larger sample size dinglan wu human ethics committees ptyf lentiviral vector
Questions {ā}
- CAR T cells for solid tumors: armed and ready to go?
- CAR T-cell therapy for solid tumors: bright future or dark reality?
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headline:Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma
description:This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. 4SCAR-T cells expanded for 1ā3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. ClinicalTrials.gov Identifier:
NCT03170141
. Registered 30 May 2017.
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headline:Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma
description:This study aimed to validate whether infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells is safe and whether CAR-T cells exert anti-glioblastoma (GBM) activity. A total of eight patients with GD2-positive GBM were enrolled and infused with autologous GD2-specific 4SCAR-T cells, either through intravenous administration alone or intravenous combined with intracavitary administration. 4SCAR-T cells expanded for 1ā3 weeks and persisted at a low frequency in peripheral blood. Of the eight evaluable patients, four showed a partial response for 3 to 24 months, three had progressive disease for 6 to 23 months, and one had stable disease for 4 months after infusion. For the entire cohort, the median overall survival was 10 months from the infusion. GD2 antigen loss and infiltrated T cells were observed in the tumor resected after infusion. Both single and combined infusions of GD2-specific 4SCAR-T cells in targeting GBM were safe and well tolerated, with no severe adverse events. In addition, GD2-specific 4SCAR-T cells partially mediate antigen loss and activate immune responses in the tumor microenvironment. Validation of our findings in a larger prospective trial is warranted. ClinicalTrials.gov Identifier:
NCT03170141
. Registered 30 May 2017.
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address:
name:School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, China
type:PostalAddress
type:Organization
name:Wen Lv
affiliation:
name:Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
address:
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
type:PostalAddress
type:Organization
name:Cheng Chen
affiliation:
name:Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
address:
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
type:PostalAddress
type:Organization
name:Kenneth King-yip Cheng
affiliation:
name:The Hong Kong Polytechnic University
address:
name:Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China
type:PostalAddress
type:Organization
name:Tao Chen
affiliation:
name:The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University
address:
name:Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China
type:PostalAddress
type:Organization
name:Southern Medical University
address:
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
type:PostalAddress
type:Organization
name:Lung-Ji Chang
affiliation:
name:Shenzhen Geno-Immune Medical Institute
address:
name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
type:PostalAddress
type:Organization
email:[email protected]
name:Dinglan Wu
affiliation:
name:The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University
address:
name:Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China
type:PostalAddress
type:Organization
name:Southern Medical University
address:
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
type:PostalAddress
type:Organization
email:[email protected]
name:Jie Mao
affiliation:
name:Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
address:
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
type:PostalAddress
type:Organization
email:[email protected]
PostalAddress:
name:Department of Neurosurgery, Shenzhen Hospital, Southern Medical University, Shenzhen, China
name:Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
name:Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
name:Department of Neurosurgery, Shenzhen Hospital, Southern Medical University, Shenzhen, China
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
name:School of Medicine, Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, China
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
name:Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China
name:Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
name:Shenzhen Key Laboratory of Viral Oncology, The Clinical Innovation & Research Centre, Shenzhen Hospital, Southern Medical University, Shenzhen, China
name:The Third School of Clinical Medicine, Southern Medical University, Shenzhen, China
name:Department of Neurosurgery, Shenzhen Peopleās Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
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