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Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma.


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.

SUBMITTER: Hu Z 

PROVIDER: S-EPMC8273876 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma.

Hu Zhuting Z   Leet Donna E DE   Allesøe Rosa L RL   Oliveira Giacomo G   Li Shuqiang S   Luoma Adrienne M AM   Liu Jinyan J   Forman Juliet J   Huang Teddy T   Iorgulescu J Bryan JB   Holden Rebecca R   Sarkizova Siranush S   Gohil Satyen H SH   Redd Robert A RA   Sun Jing J   Elagina Liudmila L   Giobbie-Hurder Anita A   Zhang Wandi W   Peter Lauren L   Ciantra Zoe Z   Rodig Scott S   Olive Oriol O   Shetty Keerthi K   Pyrdol Jason J   Uduman Mohamed M   Lee Patrick C PC   Bachireddy Pavan P   Buchbinder Elizabeth I EI   Yoon Charles H CH   Neuberg Donna D   Pentelute Bradley L BL   Hacohen Nir N   Livak Kenneth J KJ   Shukla Sachet A SA   Olsen Lars Rønn LR   Barouch Dan H DH   Wucherpfennig Kai W KW   Fritsch Edward F EF   Keskin Derin B DB   Wu Catherine J CJ   Ott Patrick A PA  

Nature medicine 20210121 3


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  ...[more]

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