NCI Spore Program

Our top-ranked team of basic scientists and translational physician-scientists pool their knowledge about brain tumors to uncover and resolve why things sometimes go wrong and how we can make them right again.
We Believe

Our top-ranked team of basic scientists and translational physician-scientists pool their knowledge about brain tumors to uncover and resolve why things sometimes go wrong and how we can make them right again.

Overview 

The Duke SPORE in Brain Cancer team is a group of basic scientists and translational physician-scientists with a strong collaborative history who are investigating novel approaches to the treatment of low grade gliomas and glioblastomas (GBMs). SPORE stands for Specialized Programs of Research Excellence. 

These treatments will potentially protect the brain from the harmful effects of traditional therapies and combat limitations that have been identified in other therapeutic approaches. The overall goal of the Duke SPORE Program is to develop new or improve existing therapies that will prolong the quality and length of life for patients with malignant brain tumors. Researchers also expect to gain a better understanding of the biology of these tumors and the patient’s response to the tumor and the therapy, as well as attract new investigators to this area of research. This SPORE encompasses four Projects, four supporting Cores, and Career Enhancement and Developmental Research Programs.  

Principal Investigators and Program Directors 

John H. Sampson, MD, PhD, MBA, MHSc 
Dr. Robert H. Wilkins and Gloria Wilkins Professor and Chair of Neurosurgery
Professor of Biomedical Engineering, Immunology, Pathology, and Radiation Oncology 
Associate Deputy Director, The Preston Robert Tisch Brain Tumor Center at Duke 

Sampson has a leadership role in the Duke Cancer Institute’s Neuro-Oncology Program, and is a recognized adviser in the surgical and experimental treatment of brain tumors, with a focus on immunotherapy and drug delivery. He has authored more than 230 peer-reviewed publications, and serves on the editorial boards of all the major journals in the field. He has received formal training in medicine, basic science research, clinical trial design and execution, and health sector management and leadership.  

Francis Ali-Osman, DSc 
Margaret Harris and David Silverman Professor of Neuro-Oncology Research 
Professor of Surgery and Pathology 

Ali-Osman is an internationally recognized biochemist and molecular biologist, and a world leader in the fields of experimental oncology, cancer therapeutics and pharmacology, and cancer-drug resistance, with a particular focus on tumors of the central nervous system. He serves on the editorial boards of several major oncology journals, as well as on several Scientific Advisory Boards, including the Board of Scientific Advisors of the National Cancer Institute (NCI). Ali-Osman has authored more than 150 peer-reviewed publications and several book chapters, and has edited two books, including one on advances in brain tumor research and therapy. 

Contact Info 
Duke University Medical Center 
Box 3050 DUMC (regular mail) 
303 Research Drive, 220 Sands Bldg (express mail)  
Durham, NC 27710 
Phone: 919.684.9041 
Fax: 919.684.9045 
Email: john.sampson@duke.edu  
 

SPORE Projects 

Project One: Intracerebrally Delivered EGFRVIII-Targeted CARs for Brain Tumors 

Project Co-Leaders:  
John H. Sampson, MD, PhD, MBA, MHSc 
Qi-Jing Li, PhD 

The overall hypothesis is that T cells transduced with EGFRvIII-targeted chimeric antigen receptors (EGFRvIII-CARs) that have been delivered intracerebrally are safe and effective. The Specific Aims are to (1) confirm that intracerebral delivery of EGFRvIII-CARs does not induce local or systemic autoimmunity, (2) establish the efficacy of intracerebrally delivered CARs against established tumors with heterogeneous EGFRvIII expression, (3) determine whether abrogation of the microRNA miR-23a in EGFRvIII-CARs enhances cytotoxicity and resistance to transforming growth factor (TGF)-mediated immunosuppression, and (4) determine the dose-limiting toxicity and maximum tolerated dose of intracerebrally injected EGFRvIII-CARs in patients with recurrent EGFRvIII positive GBMs. 

Project Two: Peptide Vaccination Targeting the Tumor-Specific IDH1 R132H Mutation for Brain Tumors 

Project Co-Leaders:  
Hai Yan, MD, PhD 
John H. Sampson, MD, PhD, MBA, MHSc 

The hypothesis is that a peptide vaccine targeting the R132H mutation of isocitrate dehydrogenase 1 (IDH1)R132H will be an effective tumor-specific therapy, without exhibiting antigen escape or toxicity,  for patients with IDH1R132H-positive gliomas. The Specific Aims are to (1) determine the cellular populations responding to IDH1R132H-specific peptide (PEPIDH1M) vaccination and optimize the immunogenicity and efficacy of PEPIDH1M , (2) perform all studies of a PEPIDH1M vaccine sufficient for an Investigational New Drug (IND) application, which will be sent to the Food and Drug Administration (FDA), and (3) conduct a pilot clinical trial to assess safety and immunogenicity of PEPIDH1M in patients with histologically proven, recurrent and resectable IDH1R132H positive grade II gliomas. 

Project Three: Peptide Vaccination Targeting the Tumor-Specific IDH1 R132H Mutation for Brain Tumors 

Project Co-Leaders:  
Michael R. Zalutsky, PhD 
Darell D. Bigner, MD, PhD 

The hypothesis is that a radiotherapeutic strategy combining the chimeric anti-tenascin-C 81C6 monoclonal antibody (ch81C6 mAb) with α -emitting Astatine-211 (211At) will stop tumor growth while sparing normal brain tissue through the highly concentrated cytotoxic radiation of 211At and the tumor-reactivity of the ch81C6 mAb. The Specific Aims are to (1) optimize 211At labeling of ch81C6 mAb with 211At at the activity levels needed for reliable dose escalation, (2) conduct a Phase 1 study of 211At-labeled ch81C6 mAb done at escalating doses of 211At (mCi) and a Phase II study done at a targeted radiation dose to the surgically created resection cavity (SCRC) margins, and (3) evaluate efficacy and normal tissue toxicity of an anti-tenascin 81C6 mAb combinatorial therapy approach utilizing the α-particle emitter 211At and either the β-particle emitter lutetium-177 (177Lu) or iodine-131 (131I). 

Project Four: Oncolytic Immunotherapy for Malignant Gliomas 

Project Co-Leaders:  
Matthias Gromeier, MD 
Allan H. Friedman, MD 

The hypothesis is that intratumoral infusion of a recombinant oncolytic poliovirus, PSVRIPO, is cytotoxic to malignant cells and establishes a pro-inflammatory activation state that enhances immune effector function. The Specific Aims are to (1) continue clinical investigation of PVSRIPO in patients with recurrent glioblastoma (GBM), (2) document immune responses in patients with GBM receiving PVSRIPO oncolytic immunotherapy, and (3) elucidate mechanisms of poliovirus oncolytic virotherapy in a transgenic syngeneic mouse glioma model. 

SPORE Cores 

Core A: Administrative Core 

Core Co-Directors: 
John H. Sampson, MD, PhD, MBA, MHSc 
Francis Ali-Osman, DSc 

The Administrative Core organizes and supports four translational research Projects, four Cores, the Developmental Research Program, and the Career Enhancement Program. It provides leadership, infrastructure, and support personnel to facilitate administrative management; promotes integration, communication, and collaboration; and ensures fiscal and regulatory compliance and an adequate patient population. Core A also develops capabilities, oversees data operations, and evaluates research progress. By serving these functions, this Core allows SPORE investigators to focus on conducting and disseminating the translational science supported by the SPORE.  

SPORE Committee and Board Members: 

The SPORE Committee and Board Members work directly with the Principal Investigators to provide general oversight and direction for SPORE investigators. Drs. Darell Bigner, Henry Friedman, Leigh Burgess, John Sampson, and Francis Ali-Osman are the Executive Committee Members, and oversee the Steering Committee, Internal Advisory Board, and External Advisory Board, all of which provide strategic oversight and means to move from concept to implementation in areas of procurement, financial management, research administration, and compliance with NCI guidelines. 

Core B: Biostatistics, Informatics, and Data Coordination Core 

Core Co-Directors: 
James E. Herndon, II, PhD 
Kouros Owzar, PhD 

This Core serves as a central resource and a supportive infrastructure for investigators involved in the Duke SPORE in Brain Cancer. The Specific Aims of this Core are to (1)  provide biostatistical leadership and expertise in the design, conduct, analysis, and reporting of Duke SPORE in Brain Cancer studies, (2)  be the SPORE data coordination center by providing secure services for electronic data acquisition, cleansing, transfer, integration, quality control, management and sharing for the Duke SPORE in Brain Cancer Projects and Cores, and (3)  develop a longitudinal brain tumor outcomes database (“datamart”) that will serve as an enduring resource for the SPORE and brain cancer research at Duke.  

Core C: Clinical Trial Operations Core 

Core Co-Directors: 
Annick Desjardins, MD, FRCPC 
James E. Herndon, II, PhD 

Core C focuses on the safe and efficient conduct of clinical studies and ensures that a diverse group of subjects are enrolled. It oversees the clinical operation of trials conducted within the SPORE, including study design and protocol preparation, patient recruitment, patient evaluation during treatment and follow-up, assessment and treatment of complications, and evaluation of patient outcomes.  Core C maintains a full portfolio of standard operating procedures (SOPs) and will align them with specific study protocols.  Core C is also  responsible for assuring that a well-trained team of clinical research staff is available to develop protocols; recruit, screen, consent, and enroll patients; conduct the clinical trials outlined in the projects; and interface with the other cores.  

Core D: Biospecimen, Pathology, and Immune Monitoring Core 

Core Co-Directors: 
Roger McLendon, MD
Kent Weinhold, PhD

The mission of the Biospecimen, Pathology and Immune Monitoring Core is to maintain a tissue bank with integrated histologic and molecular diagnostic data on all stored tissues, as well as an integrated Immune Monitoring Component Laboratory that will provide all immunologic assessments proposed for the pre-clinical and clinical studies comprising the four Projects of this SPORE.  

Career Enhancement Program 

The Career Enhancement Program (CEP) provides seed support for pilot research projects with translational potential developed by promising new and early stage investigators. Projects are encouraged to be broadly collaborative within Duke University and other institutions, and should test novel concepts and paradigms that bring new approaches into the field, which will further expand the scope of the brain tumor diagnosis, prevention, and management.  

The CEP will specifically target National Institutes of Health (NIH)-designated new investigators and early stage investigators. The CEP will focus on  projects with a high potential of developing into full SPORE projects and can replace projects within the SPORE that are not progressing satisfactorily, as well as  projects that can be leveraged into funded independent research projects using the NIH R01 or other similar mechanisms. 

Program Co-Directors: 
Mark W. Dewhirst, DVM, PhD
John H. Sampson, MD, PhD, MBA, MHSc

Grants Awarded: 

The two-step grant award process typically begins late spring, with awards being selected and announced in August.  The requests for applications will be available on this RFA webpage.

Projects Awarded (09/01/15-08/31/16) 

Principal Investigator(s) 

  • Targeting tumor and tumor-associated macrophages for glioblastoma therapy 
    Vidya Chandramohan, PhD, Assistant Professor of Pathology 
  • Bone marrow T-cell sequestration in patients and mice with GBM 
    Peter Fecci, MD, PhD, Assistant Professor of Neurosurgery 
  • Project Argo: Navigating the course between the Symplegades of tumor cell kill and normal tissue toxicity by leveraging CRISPR based screening in vitro and in vivo to discover radiosensitization targets in glioma 
    Scott Floyd, MD, PhD, Department of Radiation Oncology 

Projects Awarded (01/01/15-08/31/15) 

Principal Investigator(s) 

  • Medulloblastoma and Ependymoma Vascular characterization for targeted therapies 
    Eric M. Thompson, MD, Assistant Professor of Neurosurgery 
  • Leveraging CAR T cell induction of endogenous immunity against heterogeneous GBM 
    Luis Sanchez-Perez, PhD, Assistant Professor of Neurosurgery 
  • MTAP deletion in glioblastoma: metabolic reprogramming and therapeutic target 
    Yiping He, PhD, Assistant Professor of Pathology 

Developmental Research Program 

The Developmental Research Program (DRP) facilitates the identification and support of promising pilot research projects with translational research potential relevant to brain tumors and established by experienced investigators in other fields. Projects are encouraged to be broadly collaborative within Duke University, and also with other institutions. Projects should test novel concepts and paradigms that bring new approaches into the field and that will further expand the scope of brain tumor diagnosis, prevention, and management. The DRP will specifically target projects that have a strong likelihood of developing either into full SPORE projects, which can replace projects within the SPORE that are not progressing satisfactorily, or have been completed before the end of the SPORE funding period, or projects that can be leveraged to be funded as independent research projects using the NIH R01 or other similar funding mechanisms. The overall goal of the DRP is to identify diverse and outstanding basic and translational scientists who work in areas that are likely to significantly benefit the field of neuro-oncology and improve the diagnosis and treatment of patients with brain tumors, or contribute to the prevention of brain tumors. 

Program Co-Directors: 
Francis Ali-Osman, DSc 
John H. Sampson, MD, PhD, MBA, MHSc 

Grants Awarded: 

The two-step grant award process typically begins late spring, with awards being selected and announced in August.  The RFA will be available on this RFA webpage

 

Projects Awarded (09/01/15-08/31/16) 

Principal Investigator(s) 

  • Monocyte Vaccination to induce anti-mutant IDH1 immunity 
    Michael Dee Gunn, MD, Professor of Medicine 
  • A novel therapeutic paradigm to promote anti-tumor immune response in high grade gliomas using low-energy/low-dose radiation  
    Mark Oldham, PhD, Professor of Radiation Oncology 
  • 3-D tissue-based drug and drug target discovery assay for brain cancer 
    Donald C.Lo, PhD, Associate Professor ofNeurobiology 
  • Targeting ectopically expressed Hsp90 to discriminate and selectively ablate glioblastomas in vivo 
    Timothy Haystead, PhD, Professor of Pharmacology and Cancer Biology 

Projects Awarded (01/01/15-08/31/15) 

Principal Investigator(s) 

  • Monocyte Vaccination to induce anti-mutant IDH1 immunity 
    Michael Dee Gunn, MD, Professor of Medicine 
  • Modulating immune suppression to potentiate regional oncolytic poliovirus therapy 
    Smita K. Nair, PhD, MSc, Associate Professor of Neurosurgery 
    Matthias Gromeier, MD, Associate Professor of Neurosurgery 
  • A novel therapeutic paradigm to promote anti-tumor immune response in high grade gliomas using low-energy/low-dose radiation 
    Mark Oldham, PhD, Professor of Radiation Oncology