Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial
Name
nihms-1018546.pdf
Description
Accepted version
Size
2.48 MB
Format
Adobe PDF
Checksum (MD5)
86a218d9612f78e6e156b165e6b26491
Author(s)
Keskin, Derin B.
Anandappa, Annabelle J.
Sun, Jing
Tirosh, Itay
Mathewson, Nathan D.
Li, Shuqiang
Oliveira, Giacomo
Giobbie-Hurder, Anita
Felt, Kristen
Gjini, Evisa
Date Issued
December 2018
Journal
Nature
Publisher
Springer Science and Business Media LLC
Citation
Keskin, Derin B. et al. "Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial." Nature 565, 7738 (December 2018): 234–239 © 2018 Springer Nature Limited
Version
Author's final manuscript
Abstract
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.
MIT Department
Broad Institute of MIT and Harvard
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
http://dx.doi.org/10.1038/s41586-018-0792-9
