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

Cell Rep Med. 2024 May 21;5(5):101516. doi: 10.1016/j.xcrm.2024.101516. Epub 2024 Apr 15.

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.

Keywords: T cell responses; cell therapy; clinical trial; dendritic cell vaccine; immunotherapy; neoantigens; non-small cell lung cancer; personalized vaccine.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antigens, Neoplasm* / immunology
  • Cancer Vaccines* / immunology
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Carcinoma, Non-Small-Cell Lung* / therapy
  • Cell Differentiation* / immunology
  • Dendritic Cells* / immunology
  • Female
  • Humans
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • T-Lymphocytes* / immunology
  • Vaccination*

Substances

  • Cancer Vaccines
  • Antigens, Neoplasm