A viral-based individualized neoantigen vaccine as adjuvant treatment in resected head and neck squamous cell carcinoma: a randomized Phase I trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: In approximately one third of patients, resected head and neck squamous cell carcinoma will recur. We postulated that the induction of tumor neoantigen-specific T cell responses could prevent relapse. To this end, we developed TG4050, an individualized neoantigen therapeutic vaccine encoding up to 30 patient-specific predicted tumor neoantigens delivered by a Modified Vaccinia Ankara viral vector. We tested adjuvant TG4050 as single agent in a randomized phase I trial comparing treatment with TG4050 immediately after standard of care adjuvant therapy versus watchful waiting and treatment with TG4050 after recurrence (NCT04183166). The primary endpoint was safety, secondary endpoints included feasibility and efficacy, and immunogenicity was exploratory. TG4050 was well tolerated. Of 16 evaluable patients randomized the immediate treatment arm, none relapsed after a median follow-up of 30 months, while 3 of 16 relapsed in the control arm. T cell responses to vaccine neoantigens were detected in 73.3% of patients treated with TG4050 immediately, with a median of 3 neoantigens per responder. These responses were maintained throughout treatment and persisted for over one year after the last dose. Vaccine neoantigen-specific CD8 + T cells had an effector phenotype, displayed high expression of cytotoxic and tissue-resident markers, were polyclonal and comprised both de novo responses and amplification of pre-existing tumor-infiltrating T cell clones. Together, these translational data are consistent with the hypothesis in which single-agent delivery of TG4050 induces long-lasting tumor neoantigen-specific cytotoxic T cell responses that can prevent tumor recurrence.
Source: Nature Communications
Authors: Christian Ottensmeier, Jean-Pierre Delord, Ana Lalanne, Camille Jamet, Anne-Laure Le Gac, Katell Bidet Huang, Benoît Grellier, Jules Deforges, Maud Brandely, Eric Quéméneur, Bérangère Bastien, Annette Tavernaro, Gisèle Lacoste, Valérie Schoettel, Clémentine Spring-Giusti, Nathalie Silvestre, Jean-Baptiste Marchand, Sylvain Robin, Emmanuelle Dochy, Maurizio Ceppi, Alessandro Riva, Naoko Yamagata, Per Brattas, Kazuhide Onoguchi, Yoshiko Yamashita, Hugues Fontenelle, Mariana Eggert Martinez, Oliver Baker, Terry Jones, Andrew Schache, Eliane Piaggio, Kaïdre Bendjama, Olivier Lantz, Christophe Le Tourneau
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funder: Bpifrance
OpenAlex ID: W7203622043
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