Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma
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 have previously reported the use of an immunogenomics pipeline to identify candidate neoantigens...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-04-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1561106 |
| _version_ | 1818276947764969472 |
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| author | Tanner M. Johanns Christopher A. Miller Connor J. Liu Richard J. Perrin Diane Bender Dale K. Kobayashi Jian L. Campian Michael R. Chicoine Ralph G. Dacey Jiayi Huang Edward F. Fritsch William E. Gillanders Maxim N. Artyomov Elaine R. Mardis Robert D. Schreiber Gavin P. Dunn |
| author_facet | Tanner M. Johanns Christopher A. Miller Connor J. Liu Richard J. Perrin Diane Bender Dale K. Kobayashi Jian L. Campian Michael R. Chicoine Ralph G. Dacey Jiayi Huang Edward F. Fritsch William E. Gillanders Maxim N. Artyomov Elaine R. Mardis Robert D. Schreiber Gavin P. Dunn |
| author_sort | Tanner M. Johanns |
| collection | DOAJ |
| description | 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 have previously reported the use of an immunogenomics pipeline to identify candidate neoantigens in preclinical models of GBM. Here, we report the application of the same 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 autologous tumor lysate DC vaccination. Following vaccination, reactivity to three HLA class I- and five HLA class II-restricted candidate neoantigens were detected by IFN-γ ELISPOT in peripheral blood. A similar pattern of reactivity was observed among isolated post-treatment tumor-infiltrating lymphocytes. Genomic analysis of pre- and post-treatment GBM reflected clonal remodeling. These data demonstrate the feasibility and translational potential of a therapeutic neoantigen-based vaccine approach in patients with primary CNS tumors. |
| first_indexed | 2024-12-12T22:53:45Z |
| format | Article |
| id | doaj.art-8dde9e453942466c919f33fd089ee9d6 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-12T22:53:45Z |
| publishDate | 2019-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-8dde9e453942466c919f33fd089ee9d62022-12-22T00:09:00ZengTaylor & Francis GroupOncoImmunology2162-402X2019-04-018410.1080/2162402X.2018.15611061561106Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastomaTanner M. Johanns0Christopher A. Miller1Connor J. Liu2Richard J. Perrin3Diane Bender4Dale K. Kobayashi5Jian L. Campian6Michael R. Chicoine7Ralph G. Dacey8Jiayi Huang9Edward F. Fritsch10William E. Gillanders11Maxim N. Artyomov12Elaine R. Mardis13Robert D. Schreiber14Gavin P. Dunn15Washington University School of MedicineWashington University in St. LouisWashington University School of MedicineWashington University School of MedicineWashington University School of MedicineWashington University School of MedicineWashington University School of MedicineWashington University School of MedicineWashington University School of MedicineWashington University in St. LouisNeon TherapeuticsWashington University School of MedicineWashington University School of MedicineNationwide Children’s Hospital and The Ohio State UniversityWashington University School of MedicineWashington University School of MedicineNeoantigens 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 have previously reported the use of an immunogenomics pipeline to identify candidate neoantigens in preclinical models of GBM. Here, we report the application of the same 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 autologous tumor lysate DC vaccination. Following vaccination, reactivity to three HLA class I- and five HLA class II-restricted candidate neoantigens were detected by IFN-γ ELISPOT in peripheral blood. A similar pattern of reactivity was observed among isolated post-treatment tumor-infiltrating lymphocytes. Genomic analysis of pre- and post-treatment GBM reflected clonal remodeling. These data demonstrate the feasibility and translational potential of a therapeutic neoantigen-based vaccine approach in patients with primary CNS tumors.http://dx.doi.org/10.1080/2162402X.2018.1561106neoantigenimmunogenomicsglioblastomapersonalized vaccineclonal evolution |
| spellingShingle | Tanner M. Johanns Christopher A. Miller Connor J. Liu Richard J. Perrin Diane Bender Dale K. Kobayashi Jian L. Campian Michael R. Chicoine Ralph G. Dacey Jiayi Huang Edward F. Fritsch William E. Gillanders Maxim N. Artyomov Elaine R. Mardis Robert D. Schreiber Gavin P. Dunn Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma OncoImmunology neoantigen immunogenomics glioblastoma personalized vaccine clonal evolution |
| title | Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma |
| title_full | Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma |
| title_fullStr | Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma |
| title_full_unstemmed | Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma |
| title_short | Detection of neoantigen-specific T cells following a personalized vaccine in a patient with glioblastoma |
| title_sort | detection of neoantigen specific t cells following a personalized vaccine in a patient with glioblastoma |
| topic | neoantigen immunogenomics glioblastoma personalized vaccine clonal evolution |
| url | http://dx.doi.org/10.1080/2162402X.2018.1561106 |
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