• The Dunn Laboratory

    Washington University School of Medicine

    Department of Neurological Surgery

    Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs

  • This is a drawing

    Our Mission

    Using immunology and genomics tools, we study how the immune response to brain tumors happens. We use established preclinical models, new preclinical models we have developed, and patient-derived tissue and cells to address what T cells recognize and how antigen is presented. These studies are complemented by clinical trial efforts. Our ultimate goal is to better understand the diseases of our patients in order to develop improved therapies.

  • Select Publications

    Treatment of an Aggressive Orthotopic Murine Glioblastoma Model with Combination Checkpoint Blockade and a Multivalent Neoantigen Vaccine

    Neuro-Oncol. 2020 Mar 5;noaa050

    We characterized the microenvironment and neoantigen landscape of the aggressive CT2A GBM model in order to develop a platform to test combination checkpoint blockade and neoantigen vaccination. Whole exome DNA and RNA sequencing of the CT2A murine GBM was employed to identify expressed, somatic mutations for vaccine development. Survival analysis showed that therapeutic neoantigen vaccination with Epb4H471L, Pomgnt1R497L, and Plin2G332R, in combination with αPD-L1 treatment was superior to αPD-L1 alone. These observations provide important preclinical correlates for GBM immunotherapy trials and support further investigation into the effects of multi-modal immunotherapeutic interventions on anti-glioma immunity

     

    Read more here: https://www.ncbi.nlm.nih.gov/pubmed/32133512

    Emerging Immunotherapies for Malignant Glioma: From Immunogenomics to Cell Therapy

    Neuro Oncol. 2020 Jul 2: noaa154

    As immunotherapy assumes a central role in the management of many cancers, ongoing work is directed at understanding whether immune-based treatments will be successful in patients with glioblastoma (GBM). Despite several large studies conducted in the last several years, there remain no FDA-approved immunotherapies in this patient population. Nevertheless, there are a range of exciting new approaches being applied to GBM, all of which may not only allow us to develop new treatments but also help us understand fundamental features of the immune response in the central nervous system. In this review, we summarize new developments in the application of immune checkpoint blockade, from biomarker-driven patient selection to the timing of treatment. Moreover, we summarize novel work in personalized immune-oncology by reviewing work in cancer immunogenomics–driven neoantigen vaccine studies. Finally, we discuss cell therapy efforts by reviewing the current state of chimeric antigen receptor T-cell therapy.

     

    Read more here: https://www.ncbi.nlm.nih.gov/pubmed/32615600

    Detection of Neoantigen-specific T Cells Following a Personalized Vaccine in a Patient with Glioblastoma

    Oncoimmunology, 2019 Jan 25;8(4):e1561106

    Neoantigens represent promising targets for personalized cancer vaccine strategies. However, the feasibility of this approach in lower mutational burden tumors like glioblastoma (GBM) remains unknown. We report the application a cancer immunogenomics pipeline to identify candidate neoantigens and guide screening for neoantigen-specific T cell responses in a patient with GBM treated with a personalized synthetic long peptide vaccine. Following vaccination, reactivity to 3 HLA class I- and 5 HLA class II-restricted candidate neoantigens were detected. These data demonstrate the feasibility and translational potential of a therapeutic neoantigen-based vaccine approach in patients with primary CNS tumors.

     

    Read more here: https://www.ncbi.nlm.nih.gov/pubmed/30906654

    Targeting Neoantigens in Glioblastoma: An Overview of Cancer Immunogenomics and Translational Implications

    Neurosurgery. 2017 Sep 1;64(CN_suppl_1):165-176

    Recent interest has been focused on the identification of tumor-specific mutations, termed neoantigens, which can serve as immunodominant targets for antitumor immune effector cells to maximize “on-tumor” effect and minimize “off-tumor” toxicities. In this review, we discuss: (1) the current perspective on CNS immunosurveillance, (2) the process of neoantigen identification focusing on the cancer immunogenomics approach, and (3) how this strategy can be used to target GBM specifically.

     

    Read more here: https://www.ncbi.nlm.nih.gov/pubmed/28899059

    Immunogenomics of Hypermutated Glioblastoma: A Patient with Germline POLE Deficiency Treated with Checkpoint Blockade Immunotherapy

    Cancer Discov. 2016 Nov;6(11):1230-1236.

    We present the case of a patient with a left frontal glioblastoma with primitive neuroectodermal tumor features and hypermutated genotype in the setting of a POLE germline alteration. Using whole-exome DNA sequencing and clonal analysis, we report changes in the subclonal architecture throughout treatment. Furthermore, a persistently high neoantigen load was observed within all tumors. Interestingly, following initiation of pembrolizumab, brisk lymphocyte infiltration was observed in the subsequently resected metastatic spinal lesion and an objective radiographic response was noted in a progressive intracranial lesion, suggestive of active central nervous system (CNS) immunosurveillance following checkpoint blockade therapy.

     

    Read more here: https://www.ncbi.nlm.nih.gov/pubmed/27683556

    Endogenous Neoantigen-Specific CD8 T Cells Identified in Two Glioblastoma Models Using a Cancer Immunogenomics Approach

    Cancer Immunol Res. 2016 Dec;4(12):1007-1015

    We applied a cancer immunogenomics approach to identify tumor-specific "neoantigens" in the C57BL/6-derived GL261 and VM/Dk-derived SMA-560 tumor models. Following DNA whole-exome and RNA sequencing, high-affinity candidate neoepitopes were predicted and screened for immunogenicity by ELISPOT and tetramer analyses. We confirmed H-2Db-restricted endogenous tumor-specific neoantigens that are functionally immunogenic. By establishing the immunogenicities of predicted high-affinity neoepitopes in these models, we extend the immunogenomics-based neoantigen discovery pipeline to glioblastoma models and provide a tractable system to further study the mechanism of action of T cell-activating immunotherapeutic approaches in preclinical models of glioblastoma

     

    Read more here: https://www.ncbi.nlm.nih.gov/pubmed/27799140

  • Team Members

    Gavin P. Dunn, MD, PhD

    PI

    Associate Professor of Neurological Surgery and member of the Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs.

    Dale Kobayashi

    Staff Scientist

    Staff scientist with many years of experience in a broad range of experimental design and techniques.  Massive Blues fan.

    Jimmy Manyanga, PhD

    Postdoctoral Fellow

    Jimmy is a postdoctoral fellow who studies neoantigen discovery and targeting. Dog whisperer and excellent soccer player.

    Rupen Desai, MD

    Neurosurgery Resident

    Rupen is a neurosurgery resident who studies the use of focused ultrasound in liquid biopsy and immunotherapy. Huge Duke fan.

    Max Schaettler

    MD/PhD Student

    Max studies T cell recognition in brain tumors. He is a die-hard Bayern Munich soccer fan.

    Jay Bowman-Kirigin

    MD/PhD Student

    Jay studies antigen presentation in brain tumors and novel mouse model development. Jay is a former professional free-style skier!

    Connor Liu

    Medical Student

    Connor studies therapeutic neoantigen targeting in brain tumor models. Nobody is quite as cool as Connor.

    Andrew Coxon

    Medical Student

     

    Andrew studies T cell biology in glioblastoma.

    Mac Egan

    Medical Student

    Mac studies hypermutation in glioma. Loves California and is warming up to the Midwest!

  • Team Pictures

    Lab Holiday Dinner

    Connor receiving the trainee award at CNS 2019.

    Connor receiving Medical Student research award

    Christmas at the Chocolate Pig

    Lab lunch at Little Saigon

    Celebrating Jay's (successful) thesis Proposal

    Celebrating Tanner's paper acceptance

    Lab dinner as Connor heads back to medical school!

  • Funding

  • Contact Us

    Feel free to contact us about joining the group, donating to our efforts, or to answer any questions you have about our work.

    425 S. Euclid Ave, St Louis, MO 63110