Core C: THE IMMUNOLOGIC MONITORING AND CELLULAR PRODUCTS LABORATORY (IMCPL) will assume responsibility for providing immunologic laboratory support for all three projects in this Program Project Grant. The specific objectives of Core C will be to: 1) procure, process and bank human brain tumor or control tissue specimens as well as body fluids for all projects;2) establish human glioblastoma cell lines from tumor biopsies and maintain as well as expand these lines for preclinical studies;3) culture and evaluate characteristics of human dendritic cells (DC) for use in preclinical studies;4) generate and provide quality alpha DC1 products for therapy of patients participating in clinical trials performed as a part of the Program Project;5) perform all safety testing on therapeutic cellular products;6) perform evaluations of quality and sterility for all cultures and products designed for clinical use;7) develop, evaluate and perform monitoring assays to assess effects of immunotherapy or drug therapy on functions of immune cells, including apoptosis;8) using ELISPOT assays for IFN-gamma production, monitor changes in the frequency of antitumor CTL as a result of vaccine administration to patients with brain tumors;9) measure or serially monitor cytokines and selected growth factors in the tumor microenvironment, body fluids or in cell supernatants. To meet these diverse requirements, Core C will be organized into discrete units as follows: a) a cell production laboratory (CPL) dedicated to culture, maintenance, and evaluation of cells for human therapy (cGMP facility);b) a tissue procurement and processing laboratory (TPF);c) an immunologic monitoring and cytokine unit (IML);and d) a research laboratory for developmental preclinical studies. Core C will operate according to the FDA guidelines for preparation of biologic products for therapy (cGMP) and will maintain good laboratory practice (GLP) standards for performance of monitoring assays.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS040923-10
Application #
8377652
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Project Start
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
10
Fiscal Year
2012
Total Cost
$120,473
Indirect Cost
$40,952
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Jane, Esther P; Premkumar, Daniel R; Cavaleri, Jonathon M et al. (2016) Dinaciclib, a Cyclin-Dependent Kinase Inhibitor Promotes Proteasomal Degradation of Mcl-1 and Enhances ABT-737-Mediated Cell Death in Malignant Human Glioma Cell Lines. J Pharmacol Exp Ther 356:354-65
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2016) Antigen-specific immunoreactivity and clinical outcome following vaccination with glioma-associated antigen peptides in children with recurrent high-grade gliomas: results of a pilot study. J Neurooncol :
Pollack, Ian F; Jakacki, Regina I; Butterfield, Lisa H et al. (2016) Immune responses and outcome after vaccination with glioma-associated antigen peptides and poly-ICLC in a pilot study for pediatric recurrent low-grade gliomas. Neuro Oncol 18:1157-68
Premkumar, Daniel R; Jane, Esther P; Pollack, Ian F (2015) Cucurbitacin-I inhibits Aurora kinase A, Aurora kinase B and survivin, induces defects in cell cycle progression and promotes ABT-737-induced cell death in a caspase-independent manner in malignant human glioma cells. Cancer Biol Ther 16:233-43
Mazzacurati, Lucia; Marzulli, Marco; Reinhart, Bonnie et al. (2015) Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV. Mol Ther 23:99-107
Ceschin, R; Kurland, B F; Abberbock, S R et al. (2015) Parametric Response Mapping of Apparent Diffusion Coefficient as an Imaging Biomarker to Distinguish Pseudoprogression from True Tumor Progression in Peptide-Based Vaccine Therapy for Pediatric Diffuse Intrinsic Pontine Glioma. AJNR Am J Neuroradiol 36:2170-6
Foster, Kimberly A; Jane, Esther P; Premkumar, Daniel R et al. (2015) NVP-BKM120 potentiates apoptosis in tumor necrosis factor-related apoptosis-inducing ligand-resistant glioma cell lines via upregulation of Noxa and death receptor 5. Int J Oncol 47:506-16
Ohkuri, Takayuki; Ghosh, Arundhati; Kosaka, Akemi et al. (2014) STING contributes to antiglioma immunity via triggering type I IFN signals in the tumor microenvironment. Cancer Immunol Res 2:1199-208
Foster, Kimberly A; Jane, Esther P; Premkumar, Daniel R et al. (2014) Co-administration of ABT-737 and SAHA induces apoptosis, mediated by Noxa upregulation, Bax activation and mitochondrial dysfunction in PTEN-intact malignant human glioma cell lines. J Neurooncol 120:459-72
Pollack, Ian F (2014) Management of low-grade gliomas in childhood. World Neurosurg 81:265-7

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