Neoantigen-targeted dendritic cell vaccination in lung cancer patients induces long-lived T cells exhibiting the full differentiation spectrum

肺癌患者新抗原靶向树突状细胞疫苗接种可诱导具有全分化谱的长寿 T 细胞

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作者:Joline Ingels, Laurenz De Cock, Dieter Stevens, Rupert L Mayer, Fabien Théry, Guillem Sanchez Sanchez, David Vermijlen, Karin Weening, Saskia De Smet, Nele Lootens, Marieke Brusseel, Tasja Verstraete, Jolien Buyle, Eva Van Houtte, Pam Devreker, Kelly Heyns, Stijn De Munter, Sandra Van Lint, Glenn Go

Abstract

Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial in which a dendritic cell (DC) vaccine targeting patient-individual neoantigens is evaluated in patients with resected NSCLC. Vaccine manufacturing is feasible in six of 10 enrolled patients. Toxicity is limited to grade 1-2 adverse events. Systemic T cell responses are observed in five out of six vaccinated patients, with T cell responses remaining detectable up to 19 months post vaccination. Single-cell analysis indicates that the responsive T cell population is polyclonal and exhibits the near-entire spectrum of T cell differentiation states, including a naive-like state, but excluding exhausted cell states. Three of six vaccinated patients experience disease recurrence during the follow-up period of 2 years. Collectively, these data support the feasibility, safety, and immunogenicity of this treatment in resected NSCLC.

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