Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
- 21 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 27 (3), 515-525
- https://doi.org/10.1038/s41591-020-01206-4
Abstract
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.Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI-5 T32 CA 207021, NCI-R01 CA229261, 5 T32 CA 207021, 5 T32 CA 207021, NCI-R50 CA251956, NCI-K12CA090354, 5P30 CA006516, 5P30 CA006516, 5P30 CA006516, NCI-R50 RCA211482A, NCI-R50 CA251956, NCI P01 CA163222, R21 CA216772-01A1, NCI-U24CA224331, R01CA155010)
- Melanoma Research Alliance
- NSF Graduate Research Fellowships Program fellowship
- Kay Kendall Leukaemia Fund Fellowship
- Damon Runyon Cancer Research Foundation
- Be The Match Foundation
- American Society of Hematology
- The Free Research Fund Denmark
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