Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
Name
nihms-1707651.pdf
Description
Accepted version
Size
8.05 MB
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Unknown
Checksum (MD5)
700856a6a582072477a8a78e1c762a6c
Author(s)
Holden, Rebecca Lynn
Pentelute, Bradley L.
Barouch, Dan H.
Date Issued
2021
Journal
Nature Medicine
Publisher
Springer Science and Business Media LLC
Citation
2021. "Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma." Nature Medicine, 27 (3).
Version
Author's final manuscript
Abstract
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Personal neoantigen vaccines have been envisioned as an effective approach to induce, amplify and diversify antitumor T cell responses. To define the long-term effects of such a vaccine, we evaluated the clinical outcome and circulating immune responses of eight patients with surgically resected stage IIIB/C or IVM1a/b melanoma, at a median of almost 4 years after treatment with NeoVax, a long-peptide vaccine targeting up to 20 personal neoantigens per patient (NCT01970358). All patients were alive and six were without evidence of active disease. We observed long-term persistence of neoantigen-specific T cell responses following vaccination, with ex vivo detection of neoantigen-specific T cells exhibiting a memory phenotype. We also found diversification of neoantigen-specific T cell clones over time, with emergence of multiple T cell receptor clonotypes exhibiting distinct functional avidities. Furthermore, we detected evidence of tumor infiltration by neoantigen-specific T cell clones after vaccination and epitope spreading, suggesting on-target vaccine-induced tumor cell killing. Personal neoantigen peptide vaccines thus induce T cell responses that persist over years and broaden the spectrum of tumor-specific cytotoxicity in patients with melanoma.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
Ragon Institute of MGH, MIT and Harvard
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/S41591-020-01206-4
