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
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
Gavin P. Dunn, MD, PhD
Associate Professor of Neurological Surgery and member of the Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs.
Staff scientist with many years of experience in a broad range of experimental design and techniques.
Tanner M. Johanns, MD, PhD
Faculty, Division of Oncology
A faculty member in the Division of Oncology who treats and studies primary and metastatic brain tumors.
Max studies T cell recognition in brain tumors. He is a die-hard Bayern Munich soccer fan.
Jay studies antigen presentation in brain tumors and novel mouse model development. Jay is a former professional free-style skier.
Connor studies therapeutic neoantigen targeting in brain tumor models.
Alex has many years of experience and works closely with Dr. Johanns on T cell responses to brain tumors in preclinical models.
Andrew studies T cell biology in glioblatoma.
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!