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         headline:Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma
         description:Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies on DC phenotype and function. We investigated the ability to generate DCs using cells harvested from pediatric patients with medulloblastoma for potential evaluation of DC-RNA based vaccination approach in this patient population. Cells harvested from medulloblastoma patient leukapheresis following induction chemotherapy and granulocyte colony stimulating factor mobilization were cryopreserved prior to use in DC generation. DCs were generated from the adherent CD14+ monocytes using standard procedures and analyzed for cell recovery, phenotype and function. To summarize, 4 out of 5 patients (80 %) had sufficient monocyte recovery to permit DC generation, and we were able to generate DCs from 3 out of these 4 patient samples (75 %). Overall, we successfully generated DCs that met phenotypic requisites for DC-based cancer therapy from 3 out of 5 (60 %) patient samples and met both phenotypic and functional requisites from 2 out of 5 (40 %) patient samples. This study highlights the potential to generate functional DCs for further clinical treatments from refractory patients that have been heavily pretreated with myelosuppressive chemotherapy. Here we demonstrate the utility of evaluating the effect of the currently employed standard-of-care therapies on the ex vivo generation of DCs for DC-based clinical studies in cancer patients.
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      headline:Ex vivo generation of dendritic cells from cryopreserved, post-induction chemotherapy, mobilized leukapheresis from pediatric patients with medulloblastoma
      description:Generation of patient-derived, autologous dendritic cells (DCs) is a critical component of cancer immunotherapy with ex vivo-generated, tumor antigen-loaded DCs. An important factor in the ability to generate DCs is the potential impact of prior therapies on DC phenotype and function. We investigated the ability to generate DCs using cells harvested from pediatric patients with medulloblastoma for potential evaluation of DC-RNA based vaccination approach in this patient population. Cells harvested from medulloblastoma patient leukapheresis following induction chemotherapy and granulocyte colony stimulating factor mobilization were cryopreserved prior to use in DC generation. DCs were generated from the adherent CD14+ monocytes using standard procedures and analyzed for cell recovery, phenotype and function. To summarize, 4 out of 5 patients (80 %) had sufficient monocyte recovery to permit DC generation, and we were able to generate DCs from 3 out of these 4 patient samples (75 %). Overall, we successfully generated DCs that met phenotypic requisites for DC-based cancer therapy from 3 out of 5 (60 %) patient samples and met both phenotypic and functional requisites from 2 out of 5 (40 %) patient samples. This study highlights the potential to generate functional DCs for further clinical treatments from refractory patients that have been heavily pretreated with myelosuppressive chemotherapy. Here we demonstrate the utility of evaluating the effect of the currently employed standard-of-care therapies on the ex vivo generation of DCs for DC-based clinical studies in cancer patients.
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         Adoptive T cell therapy
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         Medulloblastoma
         Oncology
         Neurology
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      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
      name:Renee Reynolds
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:University of Buffalo
            address:
               name:Department of Neurosurgery, University of Buffalo, Buffalo, USA
               type:PostalAddress
            type:Organization
      name:Laura A. Johnson
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:University of Pennsylvania
            address:
               name:Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
               type:PostalAddress
            type:Organization
      name:Gerald Grant
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Stanford University School of Medicine
            address:
               name:Pediatric Neurosurgery, Stanford University School of Medicine, Palo Alto, USA
               type:PostalAddress
            type:Organization
      name:Herbert Fuchs
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Duke University School of Medicine
            address:
               name:Department of Pediatrics, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Preston Robert Tisch Brain Tumor Center
            address:
               name:Preston Robert Tisch Brain Tumor Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Darell D. Bigner
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Duke University School of Medicine
            address:
               name:Department of Pathology, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Preston Robert Tisch Brain Tumor Center
            address:
               name:Preston Robert Tisch Brain Tumor Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:John H. Sampson
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Duke University School of Medicine
            address:
               name:Department of Pathology, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Preston Robert Tisch Brain Tumor Center
            address:
               name:Preston Robert Tisch Brain Tumor Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Sridharan Gururangan
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Duke University School of Medicine
            address:
               name:Department of Pediatrics, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Preston Robert Tisch Brain Tumor Center
            address:
               name:Preston Robert Tisch Brain Tumor Center, Durham, USA
               type:PostalAddress
            type:Organization
      name:Duane A. Mitchell
      affiliation:
            name:Duke University School of Medicine
            address:
               name:Department of Surgery, Duke University School of Medicine, Durham, USA
               type:PostalAddress
            type:Organization
            name:Preston Robert Tisch Brain Tumor Center
            address:
               name:Preston Robert Tisch Brain Tumor Center, Durham, USA
               type:PostalAddress
            type:Organization
            name:University of Florida
            address:
               name:Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, USA
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Preston Robert Tisch Brain Tumor Center, Durham, USA
      name:Department of Pediatrics, Duke University School of Medicine, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Neurosurgery, University of Buffalo, Buffalo, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Pediatric Neurosurgery, Stanford University School of Medicine, Palo Alto, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Pediatrics, Duke University School of Medicine, Durham, USA
      name:Preston Robert Tisch Brain Tumor Center, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Pathology, Duke University School of Medicine, Durham, USA
      name:Preston Robert Tisch Brain Tumor Center, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Pathology, Duke University School of Medicine, Durham, USA
      name:Preston Robert Tisch Brain Tumor Center, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Department of Pediatrics, Duke University School of Medicine, Durham, USA
      name:Preston Robert Tisch Brain Tumor Center, Durham, USA
      name:Department of Surgery, Duke University School of Medicine, Durham, USA
      name:Preston Robert Tisch Brain Tumor Center, Durham, USA
      name:Department of Neurosurgery, Preston A. Wells, Jr. Center for Brain Tumor Therapy, University of Florida, Gainesville, USA
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