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.
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.
|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|
|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|
|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|
|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|
|Mehta, Ankit I; Brufsky, Adam M; Sampson, John H (2013) Therapeutic approaches for HER2-positive brain metastases: circumventing the blood-brain barrier. Cancer Treat Rev 39:261-9|
|Chandramohan, Vidyalakshmi; Bao, Xuhui; Kato Kaneko, Mika et al. (2013) Recombinant anti-podoplanin (NZ-1) immunotoxin for the treatment of malignant brain tumors. Int J Cancer 132:2339-48|
|Yang, Shicheng; Archer, Gary E; Flores, Catherine E et al. (2013) A cytokine cocktail directly modulates the phenotype of DC-enriched anti-tumor T cells to convey potent anti-tumor activities in a murine model. Cancer Immunol Immunother 62:1649-62|
|Piao, Hailan; Kuan, Chien-Tsun; Chandramohan, Vidya et al. (2013) Affinity-matured recombinant immunotoxin targeting gangliosides 3'-isoLM1 and 3',6'-isoLD1 on malignant gliomas. MAbs 5:748-62|
|Sanchez-Perez, Luis; Choi, Bryan D; Reap, Elizabeth A et al. (2013) BLyS levels correlate with vaccine-induced antibody titers in patients with glioblastoma lymphodepleted by therapeutic temozolomide. Cancer Immunol Immunother 62:983-7|
Showing the most recent 10 out of 115 publications