A New Plasmacytoid Dendritic Cell-Based Vaccine in Combination with Anti-PD-1 Expands the Tumor-Specific CD8+ T Cells of Lung Cancer Patients.

Autor: Hannani D; PDC*line Pharma, 38000 Grenoble, France., Leplus E; PDC*line Pharma, 38000 Grenoble, France., Laurin D; Recherche et Développement, EFS, 38000 Grenoble, France.; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France., Caulier B; Recherche et Développement, EFS, 38000 Grenoble, France.; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France., Aspord C; Recherche et Développement, EFS, 38000 Grenoble, France.; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France., Madelon N; Recherche et Développement, EFS, 38000 Grenoble, France.; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France., Bourova-Flin E; Groupe EpiMed, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France., Brambilla C; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France.; Centre Hospitalo-Universitaire Grenoble-Alpes, Université Grenoble-Alpes, 38000 Grenoble, France., Brambilla E; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France.; Centre Hospitalo-Universitaire Grenoble-Alpes, Université Grenoble-Alpes, 38000 Grenoble, France., Toffart AC; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France.; Centre Hospitalo-Universitaire Grenoble-Alpes, Université Grenoble-Alpes, 38000 Grenoble, France., Laulagnier K; PDC*line Pharma, 38000 Grenoble, France., Chaperot L; Recherche et Développement, EFS, 38000 Grenoble, France.; Institute for Advanced Biosciences, Université Grenoble-Alpes, INSERM U1209, CNRS UMR 5309, 38000 Grenoble, France., Plumas J; PDC*line Pharma, 38000 Grenoble, France.; Recherche et Développement, EFS, 38000 Grenoble, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Jan 18; Vol. 24 (3). Date of Electronic Publication: 2023 Jan 18.
DOI: 10.3390/ijms24031897
Abstrakt: The purpose of immune checkpoint inhibitor (ICI)-based therapies is to help the patient's immune system to combat tumors by restoring the immune response mediated by CD8+ cytotoxic T cells. Despite impressive clinical responses, most patients do not respond to ICIs. Therapeutic vaccines with autologous professional antigen-presenting cells, including dendritic cells, do not show yet significant clinical benefit. To improve these approaches, we have developed a new therapeutic vaccine based on an allogeneic plasmacytoid dendritic cell line (PDC*line), which efficiently activates the CD8+ T-cell response in the context of melanoma. The goal of the study is to demonstrate the potential of this platform to activate circulating tumor-specific CD8+ T cells in patients with lung cancer, specifically non-small-cell lung cancer (NSCLC). PDC*line cells loaded with peptides derived from tumor antigens are used to stimulate the peripheral blood mononuclear cells of NSCLC patients. Very interestingly, we demonstrate an efficient activation of specific T cells for at least two tumor antigens in 69% of patients irrespective of tumor antigen mRNA overexpression and NSCLC subtype. We also show, for the first time, that the antitumor CD8+ T-cell expansion is considerably improved by clinical-grade anti-PD-1 antibodies. Using PDC*line cells as an antigen presentation platform, we show that circulating antitumor CD8+ T cells from lung cancer patients can be activated, and we demonstrate the synergistic effect of anti-PD-1 on this expansion. These results are encouraging for the development of a PDC*line-based vaccine in NSCLC patients, especially in combination with ICIs.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje