This Center grant was the first Specialized Research Center on brain tumors funded by the National Institute of Neurological Diseases and Stroke. It has focused on primary and metastatic tumors of the CNS of adults and children over its 25 year history. This application represents its sixth submission for competitive review and renewal. Primary and metastatic tumors of the CNS remain significant health problems in both adults and children, and this has been the research focus of this grant in the past. However, the focus of this new competitive renewal has turned to primary CNS tumors in adults only. Research on metastatic tumors and tumors of the CNS in children will continue at the Preston Robert Tisch Brain Tumor Center at Duke, but under separate funding mechanisms. Despite intensive research efforts by many investigators, there has been little progress in uncovering etiology or improving treatment of primary brain tumors during the last 30 years. This Specialized Research Center will continue brain tumor research efforts by including an outstanding group of internationally recognized investigators with a long history of effective collaboration. In this application, primary tumors in adults, both solid intracranial tumors and neoplastic meningitis, will be approached with novel therapeutic modalities. The three research projects include Project 1, a targeted radiotherapeutic approach utilizing modular recombinant transporters (MRT) labeled with Auger electron-emitting radionuclides;Project 2 utilizes an immunological approach with temozolomide-induced lymphopenia and a multivalent vaccine;and Project 3 includes multiple translational clinical trials for primary CNS tumors. Projects 1 and 3 are continuations of projects in the current grant. Project 2 is new to this SRC. Three Cores will support these research projects. They include an IND, Regulatory, and Bioinformatics Core (Core A);a Brain Tumor Biorepository, Histopathology, and Immunologic Monitoring Core (Core B), and an Administrative Core (Core C). Cores A and C are currently funded;Core B is a continuation from earlier grant periods.

Public Health Relevance

This grant will support new and innovative approaches for the treatment of primary brain tumors in adults. Primary brain tumors remain an unmet medical need, and the likelihood of new effective treatments with acceptable toxicity should result from these efforts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS020023-29
Application #
8235934
Study Section
Special Emphasis Panel (ZNS1-SRB-G (30))
Program Officer
Fountain, Jane W
Project Start
1997-03-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
29
Fiscal Year
2012
Total Cost
$1,252,033
Indirect Cost
$432,676
Name
Duke University
Department
Pathology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Saraswathula, Anirudh; Reap, Elizabeth A; Choi, Bryan D et al. (2016) Serum elevation of B lymphocyte stimulator does not increase regulatory B cells in glioblastoma patients undergoing immunotherapy. Cancer Immunol Immunother 65:205-11
Slastnikova, Tatiana A; Rosenkranz, Andrey A; Zalutsky, Michael R et al. (2015) Modular nanotransporters for targeted intracellular delivery of drugs: folate receptors as potential targets. Curr Pharm Des 21:1227-38
Mitchell, Duane A; Batich, Kristen A; Gunn, Michael D et al. (2015) Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients. Nature 519:366-9
Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun et al. (2015) Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation. Eur J Cancer 51:969-76
Miao, Hongsheng; Choi, Bryan D; Suryadevara, Carter M et al. (2014) EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma. PLoS One 9:e94281
Killela, Patrick J; Pirozzi, Christopher J; Healy, Patrick et al. (2014) Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas. Oncotarget 5:1515-25
Choi, Bryan D; Suryadevara, Carter M; Gedeon, Patrick C et al. (2014) Intracerebral delivery of a third generation EGFRvIII-specific chimeric antigen receptor is efficacious against human glioma. J Clin Neurosci 21:189-90
Lathia, Justin D; Li, Meizhang; Sinyuk, Maksim et al. (2014) High-throughput flow cytometry screening reveals a role for junctional adhesion molecule a as a cancer stem cell maintenance factor. Cell Rep 6:117-29
Koumarianou, Eftychia; Slastnikova, Tatiana A; Pruszynski, Marek et al. (2014) Radiolabeling and in vitro evaluation of (67)Ga-NOTA-modular nanotransporter--a potential Auger electron emitting EGFR-targeted radiotherapeutic. Nucl Med Biol 41:441-9
Hodges, Tiffany R; Choi, Bryan D; Bigner, Darell D et al. (2013) Isocitrate dehydrogenase 1: what it means to the neurosurgeon: a review. J Neurosurg 118:1176-80

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