Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma.
Tanner M Johanns, Elizabeth A R Garfinkle, Katherine E Miller, Alexandra J Livingstone, Kaleigh F Roberts, Lakshmi P Rao Venkata, Joshua L Dowling, Michael R Chicoine, Ralph G Dacey, Gregory J Zipfel, Albert H Kim, Elaine R Mardis, Gavin P Dunn
Author Information
Tanner M Johanns: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri. ORCID
Elizabeth A R Garfinkle: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio. ORCID
Katherine E Miller: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio. ORCID
Alexandra J Livingstone: Division of Medical Oncology, Washington University School of Medicine, St. Louis, Missouri. ORCID
Kaleigh F Roberts: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri. ORCID
Lakshmi P Rao Venkata: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio. ORCID
Joshua L Dowling: The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. ORCID
Michael R Chicoine: Department of Neurosurgery, University of Missouri in Columbia, Columbia, Missouri. ORCID
Ralph G Dacey: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, Missouri. ORCID
Gregory J Zipfel: The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. ORCID
Albert H Kim: The Brain Tumor Center at Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. ORCID
Elaine R Mardis: The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio. ORCID
Gavin P Dunn: Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts. ORCID
PURPOSE: Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax. PATIENTS AND METHODS: In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209). RESULTS: Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFN��-ELISPOT assay. A statistically significant increase in IFN�� producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells. CONCLUSIONS: Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine-based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM.
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