The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
Open accessAbstract
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. 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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Metadata
- Authors
- Hu, Z., Leet, D. E., Allesøe, R. L., Oliveira, G., Li, S., Luoma, A. M., Liu, J., Forman, J., Huang, T., Iorgulescu, J. B., Holden, R., Sarkizova, S., Gohil, S. H., Redd, R. A., Sun, J., Elagina, L., Giobbie-Hurder, A., Zhang, W., Peter, L., Ciantra, Z., Rodig, S., Olive, O., Shetty, K., Pyrdol, J., Uduman, M., Lee, P. C., Bachireddy, P., Buchbinder, E. I., Yoon, C. H., Neuberg, D., Pentelute, B. L., Hacohen, N., Livak, K. J., Shukla, S. A., Olsen, L. R., Barouch, D. H., Wucherpfennig, K. W., Fritsch, E. F., Keskin, D. B., Wu, C. J., & Ott, P. A.
- Venue
- Nature Medicine
- Published
- 2021-01-21
- Volume
- 27
- Issue
- 3
- Pages
- 515-525
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3122472315
- Cited by
- 538
- References
- 45
- FWCI
- 25.21
- Type
- journal article
- Language
- en
- Open access
- green
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- Hu, Z., Leet, D. E., Allesøe, R. L., Oliveira, G., Li, S., Luoma, A. M., Liu, J., Forman, J., Huang, T., Iorgulescu, J. B., Holden, R., Sarkizova, S., Gohil, S. H., Redd, R. A., Sun, J., Elagina, L., Giobbie-Hurder, A., Zhang, W., Peter, L., . . . Ott, P. A. (2021). Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma. Nature Medicine. https://doi.org/10.1038/s41591-020-01206-4
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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