A real-world observation of patients with glioblastoma treated with a personalized peptide vaccine

Pauline Latzer, Henning Zelba, Florian Battke, Annekathrin Reinhardt, Borong Shao, Oliver Bartsch, Armin Rabsteyn, Johannes Harter, Martin Schulze, Thomas Okech, Alexander Golf, Christina Kyzirakos-Feger, Simone Kayser, Natalia Pieper, Magdalena Feldhahn, Julian Wünsche, Christian Seitz, Dirk Hadaschik, Claus Garbe, Till-Karsten Hauser, Christian Fougère, Dirk Biskup, Dawn Brooke, David Parker, Uwe M. Martens, Gerald Illerhaus, Deborah T. Blumenthal, Ryan Merrell, Luisa Sánchez Lorenzo, Máté Hidvégi, Paula Robles, Sied Kebir, William W. Li, Vincent W. Li, Matthew Williams, Alexandra M. Miller, Santosh Kesari, Michael Castro, Annick Desjardins, David M. Ashley, Henry S. Friedman, Patrick Y. Wen, Elisabeth C. Neil, Fabio M. Iwamoto, Bence Sipos, Karsten Geletneky, Lars Zender, Martin Glas, David A. Reardon and Saskia Biskup ()
Additional contact information
Pauline Latzer: Zentrum für Humangenetik Tübingen
Henning Zelba: Zentrum für Humangenetik Tübingen
Florian Battke: CeGaT GmbH
Annekathrin Reinhardt: Zentrum für Humangenetik Tübingen
Borong Shao: Zentrum für Humangenetik Tübingen
Oliver Bartsch: Zentrum für Humangenetik Tübingen
Armin Rabsteyn: Zentrum für Humangenetik Tübingen
Johannes Harter: CeGaT GmbH
Martin Schulze: Zentrum für Humangenetik Tübingen
Thomas Okech: MVZ Zentrum für ambulante Onkologie GmbH
Alexander Golf: MVZ Zentrum für ambulante Onkologie GmbH
Christina Kyzirakos-Feger: Zentrum für Humangenetik Tübingen
Simone Kayser: Zentrum für Humangenetik Tübingen
Natalia Pieper: Zentrum für Humangenetik Tübingen
Magdalena Feldhahn: CeGaT GmbH
Julian Wünsche: Zentrum für Humangenetik Tübingen
Christian Seitz: KiTZ, Hopp Children’s Cancer Center
Dirk Hadaschik: CeCaVa GmbH
Claus Garbe: University Hospital Tübingen
Till-Karsten Hauser: Universitätsklinikum Tübingen
Christian Fougère: Universitätsklinikum Tübingen
Dirk Biskup: CeGaT GmbH
Dawn Brooke: Provenance Precision Medicine Foundation
David Parker: PHM
Uwe M. Martens: Cancer Center Heilbronn-Franken, SLK Kliniken GmbH
Gerald Illerhaus: Klinikum Stuttgart
Deborah T. Blumenthal: Tel-Aviv University
Ryan Merrell: Vanderbilt University Medical Center
Luisa Sánchez Lorenzo: Clínica Universidad de Navarra
Máté Hidvégi: Jewish Theological Seminary—University of Jewish Studies (OR-ZSE)
Paula Robles: University of Calgary
Sied Kebir: Universitätsklinikum Essen
William W. Li: Angiogenesis Foundation
Vincent W. Li: Angiogenesis Foundation
Matthew Williams: NHS London
Alexandra M. Miller: NYU Langone Health’s Perlmutter Cancer Center
Santosh Kesari: Providence Saint John’s Health Center
Michael Castro: Cellworks Group Inc
Annick Desjardins: Duke University Medical Center
David M. Ashley: Duke University Medical Center
Henry S. Friedman: Duke University Medical Center
Patrick Y. Wen: Harvard Medical School
Elisabeth C. Neil: University of Minnesota Health
Fabio M. Iwamoto: Columbia University Medical Center
Bence Sipos: Molekularpathologie Baden-Württemberg GbR
Karsten Geletneky: Klinikum Darmstadt GmbH
Lars Zender: Internal Medicine VIII
Martin Glas: Universitätsklinikum Essen Klinik für Neurologie
David A. Reardon: Harvard Medical School
Saskia Biskup: Zentrum für Humangenetik Tübingen

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: Abstract Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0–36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.

Date: 2024
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DOI: 10.1038/s41467-024-51315-8

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