? Biorepository, Pathology, and Immune Monitoring Core (Core 3) The Biorepository, Pathology, and Immune Monitoring Core (Core 3) will serve as a critical resource for the three projects and developmental programs of this SPORE in Brain Cancer by providing comprehensive biorepository banking, complete phenotypic and genotypic histopathologic assessment, and state-of-the-art immune monitoring. This resource will be provided by a team of highly accomplished research scientists who have decades of experience with these platforms in conjunction with previous and current cancer immunotherapy trials. Our Biorepository resource has accumulated over 33,000 frozen tumor blocks, including over 21,000 paired central nervous system tumor samples, in -170oC storage with matched blood samples from over 2,687 patients. The staff are trained in Good Laboratory Practices (GLP) and the Biorepository is certified by the College of American Pathologists. Samples are linked with Duke Hospital Pathology reports that include a profile of diagnostic, proliferative, phenotypic, and genotypic data in order that researchers have access to well characterized tumor tissues. This Core also has an extensive history of human immune profiling using highly standardized and validated assays at Duke, thus providing a broad repertoire of state-of-the-art technology platforms to comprehensively interrogate immune responses to immunotherapy. The flow cytometry-based phenotypic and functional immune profiling platforms represent a particular strength in this proposal, based on the extensive past and ongoing applications as well as refinements of these tools in the context of vaccine and cancer immunotherapy trials and proficiency testing efforts. Additionally, all immune monitoring of SPORE-associated clinical trials will be performed according to Good Clinical Laboratory Practices (GCLP).
The specific aims are 1) To provide blood and tissue distribution and tracking services, tissue diagnosis, immunohistochemical (IHC) and biobanking support to the Projects' clinical and correlative studies. 2) To provide GCLP-compliant, comprehensive Immune Monitoring of patients enrolled in the Projects' clinical studies using standardized and validated state-of-the-art flow cytometry-based immune profiling platforms. This Core will also continue to innovate, including by translating innovative methodologies developed to analyze brain tumoral heterogeneity and immune responses in this Core into diagnostic, prognostic, and therapeutic responsiveness clinical tests for the bedside. In addition the Inter-SPORE consortium for immune monitoring will continue to share development and validation of new immune profiling platforms while also attempting to standardize all aspects of specimen acquisition, preparation, transport, and evaluation according to a uniform set of Standard Operating Procedures (SOPs).

Public Health Relevance

? Biorepository, Pathology, and Immune Monitoring Core (Core 3) Malignant primary brain tumors are generally fatal, with devastating consequences for patients and their families. The Duke SPORE in Brain Cancer proposes a coordinated program of scientific discovery and translational research to enhance treatment of brain tumors and minimize their sequelae. In support of the SPORE?s goals and both pre-clinical and clinical research activities, this Biorepository, Pathology, and Immune Monitoring Core provides scientific leadership as well as comprehensive and state-of-the-art biospecimen, pathologic, and immune monitoring support.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA190991-06
Application #
9632610
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Ding, Yi; Gong, Chang; Huang, De et al. (2018) Synthetic lethality between HER2 and transaldolase in intrinsically resistant HER2-positive breast cancers. Nat Commun 9:4274
Dobrikov, Mikhail I; Dobrikova, Elena Y; Gromeier, Matthias (2018) Ribosomal RACK1:Protein Kinase C ?II Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation. Mol Cell Biol 38:
Desjardins, Annick; Gromeier, Matthias; Herndon 2nd, James E et al. (2018) Recurrent Glioblastoma Treated with Recombinant Poliovirus. N Engl J Med 379:150-161
Gromeier, Matthias; Nair, Smita K (2018) Recombinant Poliovirus for Cancer Immunotherapy. Annu Rev Med 69:289-299
Lin, Jiaxing; Gresham, Jeremy; Wang, Tongrong et al. (2018) bcSeq: an R package for fast sequence mapping in high-throughput shRNA and CRISPR screens. Bioinformatics 34:3581-3583
Swartz, Adam M; Reap, Elizabeth; Norberg, Pamela et al. (2018) A simple and enzyme-free method for processing infiltrating lymphocytes from small mouse tumors for ELISpot analysis. J Immunol Methods 459:90-93
Chong, Mengyang; Yin, Tao; Chen, Rui et al. (2018) CD36 initiates the secretory phenotype during the establishment of cellular senescence. EMBO Rep 19:
Thompson, Eric M; Brown, Michael; Dobrikova, Elena et al. (2018) Poliovirus Receptor (CD155) Expression in Pediatric Brain Tumors Mediates Oncolysis of Medulloblastoma and Pleomorphic Xanthoastrocytoma. J Neuropathol Exp Neurol 77:696-702
Woroniecka, Karolina; Chongsathidkiet, Pakawat; Rhodin, Kristen et al. (2018) T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma. Clin Cancer Res 24:4175-4186
Woroniecka, Karolina I; Rhodin, Kristen E; Chongsathidkiet, Pakawat et al. (2018) T-cell Dysfunction in Glioblastoma: Applying a New Framework. Clin Cancer Res 24:3792-3802

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