Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial

Research output: Contribution to journalLetter – Annual report year: 2018Researchpeer-review

  • Author: Keskin, Derin B.

    Dana-Farber Cancer Institute, United States

  • Author: Anandappa, Annabelle J.

    Dana-Farber Cancer Institute, United States

  • Author: Sun, Jing

    Dana-Farber Cancer Institute, United States

  • Author: Tirosh, Itay

    Broad Institute, United States

  • Author: Mathewson, Nathan D.

    Harvard Medical School, United States

  • Author: Li, Shuqiang

    Broad Institute, United States

  • Author: Oliveira, Giacomo

    Dana-Farber Cancer Institute, United States

  • Author: Giobbie-Hurder, Anita

    Dana-Farber Cancer Institute, United States

  • Author: Felt, Kristen

    Dana-Farber Cancer Institute, United States

  • Author: Gjini, Evisa

    Dana-Farber Cancer Institute, United States

  • Author: Shukla, Sachet A

    Dana-Farber Cancer Institute, United States

  • Author: Hu, Zhuting

    Dana-Farber Cancer Institute, United States

  • Author: Li, Letitia

    Dana-Farber Cancer Institute, United States

  • Author: Le, Phuong M.

    Dana-Farber Cancer Institute, United States

  • Author: Allesøe, Rosa Lundbye

    Genomic Epidemiology, Department of Bio and Health Informatics, Technical University of Denmark, Denmark

  • Author: Richman, Alyssa R.

    Broad Institute, United States

  • Author: Kowalczyk, Monika S

    Broad Institute, United States

  • Author: Abdelrahman, Sara

    Dana-Farber Cancer Institute, United States

  • Author: Geduldig, Jack E.

    Dana-Farber Cancer Institute, United States

  • Author: Charbonneau, Sarah

    Dana-Farber Cancer Institute, United States

  • Author: Pelton, Kristine

    Dana-Farber Cancer Institute, United States

  • Author: Iorgulescu, J. Bryan

    Dana-Farber Cancer Institute, United States

  • Author: Elagina, Liudmila

    Broad Institute, United States

  • Author: Zhang, Wandi

    Dana-Farber Cancer Institute, United States

  • Author: Olive, Oriol

    Dana-Farber Cancer Institute, United States

  • Author: McCluskey, Christine

    Dana-Farber Cancer Institute, United States

  • Author: Olsen, Lars Rønn

    Cancer Genomics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Stevens, Jonathan

    Brigham and Women's Hospital, United States

  • Author: Lane, William J.

    Harvard Medical School

  • Author: Salazar, Andres M.

    Oncovir Inc., United States

  • Author: Daley, Heather

    Dana-Farber Cancer Institute, United States

  • Author: Wen, Patrick Y.

    Dana-Farber Cancer Institute, United States

  • Author: Chiocca, E. Antonio

    Harvard Medical School

  • Author: Harden, Maegan

    Broad Institute, United States

  • Author: Lennon, Niall J.

    Broad Institute, United States

  • Author: Gabriel, Stacey

    Broad Institute, United States

  • Author: Getz, Gad

    Broad Institute, United States

  • Author: Lander, Eric S.

    Broad Institute, United States

  • Author: Regev, Aviv

    Broad Institute, United States

  • Author: Ritz, Jerome

    Dana-Farber Cancer Institute, United States

  • Author: Neuberg, Donna

    Dana-Farber Cancer Institute, United States

  • Author: Rodig, Scott J.

    Harvard Medical School

  • Author: Ligon, Keith L.

    Broad Institute, United States

  • Author: Suvà, Mario L.

    Broad Institute, United States

  • Author: Wucherpfennig, Kai W.

    Harvard Medical School, United States

  • Author: Hacohen, Nir

    Broad Institute, United States

  • Author: Fritsch, Edward F.

    Dana-Farber Cancer Institute, United States

  • Author: Livak, Kenneth J

    Dana-Farber Cancer Institute, United States

  • Author: Ott, Patrick A

    Dana-Farber Cancer Institute, United States

  • Author: Wu, Catherine J

    Dana-Farber Cancer Institute, United States

  • Author: Reardon, David A.

    Dana-Farber Cancer Institute, United States

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Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumour rejection3. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma4-6, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load1,7 and an immunologically 'cold' tumour microenvironment8. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.
Original languageEnglish
JournalNature
Volume565
Pages (from-to)234-239
Number of pages4
ISSN0028-0836
DOIs
Publication statusPublished - 2018
CitationsWeb of Science® Times Cited: No match on DOI
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