Journal
NATURE MEDICINE
Volume 27, Issue 3, Pages 515-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-020-01206-4
Keywords
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Funding
- National Institutes of Health [NCI-R50 CA251956, NCI-R01 CA229261, NCI P01 CA163222, NCI-R01 CA238039, 5P30 CA006516, NCI-K12CA090354]
- Team Science Award from the Melanoma Research Alliance
- Francis and Adele Kittredge Family Immuno-Oncology and Melanoma Research Fund
- Faircloth Family Research Fund
- Bender Family Research Fund
- DFCI Center for Cancer Immunotherapy Research fellowship
- Damon Runyon Cancer Research Foundation
- Be The Match Foundation
- American Society of Hematology Fellow Scholar Award
- NSF Graduate Research Fellowships Program fellowship
- Kay Kendall Leukaemia Fund Fellowship
- Free Research Fund Denmark [8048-00078A]
- G. Harold and Leila Y. Mathers Foundation
- Koch Institute for Integrative Cancer Research at MIT
- Dana-Farber/Harvard Cancer Center
- Howard Hughes Medical Institute Medical Research Fellows Program
- Novo Nordisk Foundation [NNF14CC0001]
- National Institutes of Health (NIH/NCI) [R21 CA216772-01A1, NCI-SPORE-2P50CA101942-11A1, U24CA224331, R01CA155010, NCI-R50 RCA211482A]
- [5 T32 CA 207021-3]
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Personal neoantigen peptide vaccines induce long-lasting T cell responses in melanoma patients, broadening the spectrum of tumor-specific cytotoxicity and resulting in diverse T cell clones with cytotoxic gene signatures.
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 (). 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. Personalized neoantigen vaccination in patients with melanoma elicits durable and specific memory T cell clones that have cytotoxic gene signatures and can diversify to include nonvaccine neoantigen specificities.
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