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D'Alise, Anna Morena; Leoni, Guido; Cotugno, Gabriella; Siani, Loredana; Vitale, Rosa; Ruzza, Valentino; Garzia, Irene; Antonucci, Laura; Micarelli, Elisa; Venafra, Veronica; Gogov, Sven; Capone, Alessia; Runswick, Sarah; Martin-Liberal, Juan; Calvo, Emiliano; Moreno, Victor; Symeonides, Stefan N.; Scarselli, Elisa; Bechter, Oliver

Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses

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  • Medientyp: E-Artikel
  • Titel: Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses
  • Beteiligte: D'Alise, Anna Morena; Leoni, Guido; Cotugno, Gabriella; Siani, Loredana; Vitale, Rosa; Ruzza, Valentino; Garzia, Irene; Antonucci, Laura; Micarelli, Elisa; Venafra, Veronica; Gogov, Sven; Capone, Alessia; Runswick, Sarah; Martin-Liberal, Juan; Calvo, Emiliano; Moreno, Victor; Symeonides, Stefan N.; Scarselli, Elisa; Bechter, Oliver
  • Erschienen: American Association for Cancer Research (AACR), 2024
  • Erschienen in: Clinical Cancer Research (2024), Seite OF1-OF12
  • Sprache: Englisch
  • DOI: 10.1158/1078-0432.ccr-23-3940
  • ISSN: 1557-3265; 1078-0432
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats:p>Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T-cell response to overcome tumor heterogeneity. NOUS-PEV is a vector-based personalized vaccine, expressing 60 nAgs and consists of priming with a nonhuman Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara. Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment-naïve patients with metastatic melanoma (NCT04990479).</jats:p> </jats:sec> <jats:sec> <jats:title>Patients and Methods:</jats:title> <jats:p>The feasibility of this approach was demonstrated by producing, releasing, and administering to 6 patients 11 of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen-specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced T-cell receptor (TCR) clonotypes was observed in the posttreatment biopsies of patients with clinical response, providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cells.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor-reactive T cells to empower a diverse, potent, and durable antitumor immune response. Finally, a gene signature indicative of the reduced presence of activated T cells together with very poor expression of the antigen-processing machinery genes has been identified in pretreatment biopsies as a potential biomarker of resistance to the treatment.</jats:p> </jats:sec>