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Topics {✒️}

4scar-gd2-modified t-cell therapy 4scar-gd2 t-cell-treated patients 4scar-gd2 t-cell infusions 4scar-gd2 t-cell therapy 4scar-gd2 t-cell expansion 4scar-gd2 t-cell infusion 4scar-gd2 t-cell administration autologous car-t-cell therapy high-affinity gd2-specific car 4scar-gd2 t-cell treatment 4scar-gd2 t-cell persistence lung-ji chang high-affinity gd2 car-response confirm t-cell purity anti-gd2 antibody therapy car t-cell therapy car t-cell counts car t-cell engineering toxic event-related death full size image article download pdf car t-cell expansion anti-hcd4 pacific blue anti-hcd8 percp-cy5 gd2-chimeric antigen receptor coexpress tumor-specific receptors car t-cell infusion anti-hcd8 pe-cy7 car t-cell studies anti-gd2 monoclonal antibodies b-cell lymphoblastic leukemia national cancer institute nhp/tyf lentiviral vector lentiviral 4scar-gd2 vector cd28/4-1bb/cd3ζ-icasp9 chimeric antigen receptor-positive quality control/assurance assay 123i‐mibg scans evaluation immune-compromised leukemic patient antibody-conjugated magnetic beads 3rd-generation car incorporating received 123i‐mibg scans interleukin-15-derived dendritic cells t-cell products generation gd2-car ebvst modified 4scar-gd2 clinical oncology aims anti-gd2 antibody t-cell expansion 4scar-gd2 car design

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         headline:GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients
         description:This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3–4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00–59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25–15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1–2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.
         datePublished:2021-11-01T00:00:00Z
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            CAR T
            Immunotherapy
            Pediatric
            GD2
            Oncology
            Cancer Research
            Internal Medicine
            Hematology
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      headline:GD2-specific chimeric antigen receptor-modified T cells for the treatment of refractory and/or recurrent neuroblastoma in pediatric patients
      description:This study aimed to evaluate the safety and efficacy of chimeric antigen receptor (CAR) disialoganglioside 2 (GD2)-specific (4SCAR-GD2) T cells for treatment of refractory and/or recurrent neuroblastoma (NB) in pediatric patients. A phase I clinical study using 4SCAR-GD2 T cells for the treatment of NB in pediatric patients was conducted. This study was registered at www.clinicaltrials.gov (NCT02765243). A lentiviral CAR with the signaling domains of CD28/4-1BB/CD3ζ-iCasp9 was transduced into activated T cells. The response to 4SCAR-GD2 T-cell treatment, and 4SCAR-GD2 T-cell expansion and persistence in patients were evaluated. Toxicities were determined based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Twelve patients were enrolled and finally ten patients were included in this clinical trial which started from January 1, 2016, to August 1, 2017. These patients had progressive disease (PD) before CAR T-cell infusion. After 4SCAR-GD2 T-cell treatment, 6 (6/10) had stable disease (SD) at 6 months, and 4 (4/10) remained SD at 1 year and alive after 3–4 years of follow-up. Six patients died due to disease progression by the end of July 1, 2020. The median overall survival (OS) time was 25 months (95% CI, 0.00–59.43), and the median progression-free survival (PFS) time was 8 months (95% CI, 0.25–15.75). Grade 3 or 4 hematological toxicities were the common adverse events frequently occurred after fludarabine and cyclophosphamide (Flu/cy) chemotherapy. Grade 1–2 toxicities such as cytokine release syndrome (CRS) and neuropathic pain were common, but were transient and mild. The 4SCAR-GD2 T-cell therapy demonstrated antitumor effect and manageable toxicities, indicating its potential to benefit children with refractory and/or recurrent NB.
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      dateModified:2021-11-01T00:00:00Z
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      keywords:
         Neuroblastoma
         CAR T
         Immunotherapy
         Pediatric
         GD2
         Oncology
         Cancer Research
         Internal Medicine
         Hematology
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            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Li Wu
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Xu Liao
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Jiale Liu
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Yinghua Zeng
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Lichan Liang
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Guanmei Zhang
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Bin Wang
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Neonatology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Zhu Wu
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Intensive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Shaohua Tao
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Intensive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Yuchen Liu
      affiliation:
            name:Shenzhen Geno-Immune Medical Institute
            address:
               name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
               type:PostalAddress
            type:Organization
      name:Cheng Jiao
      affiliation:
            name:Shenzhen Geno-Immune Medical Institute
            address:
               name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
               type:PostalAddress
            type:Organization
      name:Lung-Ji Chang
      url:http://orcid.org/0000-0003-2395-5216
      affiliation:
            name:Shenzhen Geno-Immune Medical Institute
            address:
               name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Lihua Yang
      url:http://orcid.org/0000-0002-0009-871X
      affiliation:
            name:Zhujiang Hospital, Southern Medical University
            address:
               name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Neonatology, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Intensive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Pediatric Intensive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
      name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
      name:Shenzhen Geno-Immune Medical Institute, Shenzhen, China
      name:Department of Pediatric Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China

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