Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma
Menée sur 8 patients atteints d'un mélanome de stade IIIB/C ou IVM1a/b, cette étude démontre qu'un vaccin personnalisé ciblant 20 antigènes tumoraux favorise la persistance de la réponse antitumorale de lymphocytes T mémoire et le développement d'une réponse immunitaire contre des épitopes autres que ceux ciblés par le vaccin (processus dit "epitope spreading")
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.
Nature Medicine 2021