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

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 Goetgeluk; Sarah Bonte; Lore Billiet; Melissa Pille; Hanne Jansen; Eva Pascal; Lucas Deseins; Lies Vantomme; Maarten Verdonckt; Ria Roelandt; Thomas Eekhout; Niels Vandamme; Georges Leclercq; Tom Taghon; Tessa Kerre; Floris Vanommeslaeghe; Annemieke Dhondt; Liesbeth Ferdinande; Jo Van Dorpe; Liesbeth Desender; Frederic De Ryck; Frank Vermassen; Veerle Surmont; Francis Impens; Björn Menten; Karim Vermaelen; Bart Vandekerckhove

doi:10.1016/j.xcrm.2024.101516

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

Cell Rep Med. 2024 Apr 9:101516. doi: 10.1016/j.xcrm.2024.101516. Online ahead of print.

Authors

Joline Ingels¹, Laurenz De Cock², Dieter Stevens³, Rupert L Mayer⁴, Fabien Théry⁵, Guillem Sanchez Sanchez⁶, David Vermijlen⁶, Karin Weening⁷, Saskia De Smet⁸, Nele Lootens⁸, Marieke Brusseel⁸, Tasja Verstraete⁹, Jolien Buyle⁹, Eva Van Houtte⁸, Pam Devreker⁸, Kelly Heyns⁸, Stijn De Munter¹, Sandra Van Lint³, Glenn Goetgeluk⁷, Sarah Bonte¹⁰, Lore Billiet¹, Melissa Pille⁷, Hanne Jansen⁷, Eva Pascal¹, Lucas Deseins¹, Lies Vantomme¹¹, Maarten Verdonckt⁷, Ria Roelandt¹², Thomas Eekhout¹², Niels Vandamme¹², Georges Leclercq⁷, Tom Taghon⁷, Tessa Kerre¹³, Floris Vanommeslaeghe¹⁴, Annemieke Dhondt¹⁴, Liesbeth Ferdinande¹⁵, Jo Van Dorpe¹⁵, Liesbeth Desender¹⁶, Frederic De Ryck¹⁶, Frank Vermassen¹⁶, Veerle Surmont⁹, Francis Impens⁵, Björn Menten², Karim Vermaelen¹⁷, Bart Vandekerckhove¹⁸

Affiliations

¹ Department of Diagnostic Sciences, Ghent University, 9000 Ghent, East-Flanders, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium.
² Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; Department of Biomolecular Medicine, Ghent University, 9000 Ghent, East-Flanders, Belgium.
³ Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; Respiratory Medicine, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium.
⁴ Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; Department of Biomolecular Medicine, Ghent University, 9000 Ghent, East-Flanders, Belgium; VIB-UGent Center for Medical Biotechnology, VIB, 9000 Ghent, East-Flanders, Belgium.
⁵ Department of Biomolecular Medicine, Ghent University, 9000 Ghent, East-Flanders, Belgium; VIB-UGent Center for Medical Biotechnology, VIB, 9000 Ghent, East-Flanders, Belgium.
⁶ Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles, 1050 Brussels, Brussels, Belgium; Institute for Medical Immunology, Université Libre de Bruxelles, 1050 Brussels, Brussels, Belgium; Université Libre de Bruxelles Center for Research in Immunology, Université Libre de Bruxelles, 1050 Brussels, Brussels, Belgium; WELBIO Department, WEL Research Institute, 1300 Wavre, Walloon Brabant, Belgium.
⁷ Department of Diagnostic Sciences, Ghent University, 9000 Ghent, East-Flanders, Belgium.
⁸ GMP Unit Cell Therapy, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium.
⁹ Respiratory Medicine, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium.
¹⁰ Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; VIB-UGent Center for Medical Biotechnology, VIB, 9000 Ghent, East-Flanders, Belgium.
¹¹ Department of Biomolecular Medicine, Ghent University, 9000 Ghent, East-Flanders, Belgium.
¹² VIB Single Cell Core, VIB, 9000/3000 Ghent/Leuven, East-Flanders/Flemish Brabant, Belgium.
¹³ Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; VIB-UGent Center for Medical Biotechnology, VIB, 9000 Ghent, East-Flanders, Belgium; Hematology, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium.
¹⁴ Nephrology, Ghent University Hospital, Ghent University, 9000 Ghent, East-Flanders, Belgium.
¹⁵ Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; Pathology, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium.
¹⁶ Thoracic and Vascular Surgery, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium.
¹⁷ Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; Respiratory Medicine, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium. Electronic address: karim.vermaelen@ugent.be.
¹⁸ Department of Diagnostic Sciences, Ghent University, 9000 Ghent, East-Flanders, Belgium; Cancer Research Institute Ghent (CRIG), 9000 Ghent, Easy-Flanders, Belgium; GMP Unit Cell Therapy, Ghent University Hospital, 9000 Ghent, East-Flanders, Belgium. Electronic address: bart.vandekerckhove@ugent.be.

PMID: 38626769
DOI: 10.1016/j.xcrm.2024.101516

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.