Journal article
Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
Dana-Farber Cancer Institute1
Harvard University2
University of Copenhagen3
Broad Institute of Harvard University and Massachusetts Institute of Technology4
Massachusetts Institute of Technology5
University College London6
Department of Health Technology, Technical University of Denmark7
Bioinformatics, Department of Health Technology, Technical University of Denmark8
Single Cell Omics, Bioinformatics, Department of Health Technology, Technical University of Denmark9
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.
Language: | English |
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Publisher: | Nature Publishing Group US |
Year: | 2021 |
Pages: | 515-525 |
ISSN: | 1546170x and 10788956 |
Types: | Journal article |
DOI: | 10.1038/s41591-020-01206-4 |
ORCIDs: | 0000-0002-4494-1705 , 0000-0003-1405-3667 , 0000-0002-1329-5288 , 0000-0002-2105-7503 , 0000-0002-7242-801X , 0000-0001-9105-5856 , 0000-0001-5127-4659 , 0000-0002-8412-5665 , 0000-0002-3348-5054 , 0000-0002-4253-943X and Olsen, Lars Rønn |