Pauline Latzer 1, Henning Zelba 1, Florian Battke 2, Annekathrin Reinhardt 1, Borong Shao 1, Oliver Bartsch 1, Armin Rabsteyn 1, Johannes Harter 2, Martin Schulze 1, Thomas Okech 3, Alexander Golf 3, Christina Kyzirakos-Feger 1, Simone Kayser 1, Natalia Pieper 1, Magdalena Feldhahn 2, Julian Wünsche 1 3, Christian Seitz 4, Dirk Hadaschik 5, Claus Garbe 6, Till-Karsten Hauser 7, Christian la Fougère 8, Dirk Biskup 2, Dawn Brooke 9, David Parker 10, Uwe M Martens 11, Gerald Illerhaus 12, Deborah T Blumenthal 13, Ryan Merrell 14, Luisa Sánchez Lorenzo 15, Máté Hidvégi 16, Paula de Robles 17 18, Sied Kebir 19, William W Li 20, Vincent W Li 20 21, Matthew Williams 22, Alexandra M Miller 23, Santosh Kesari 24, Michael Castro 25 26, Annick Desjardins 27, David M Ashley 27 28, Henry S Friedman 27, Patrick Y Wen 29, Elisabeth C Neil 30, Fabio M Iwamoto 31, Bence Sipos 32, Karsten Geletneky 33, Lars Zender 34, Martin Glas 35, David A Reardon 29, Saskia Biskup 36 37

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.

© 2024. The Author(s).

  1. Zentrum für Humangenetik Tübingen, Tübingen, Germany.
  2. CeGaT GmbH, Tübingen, Germany.
  3. MVZ Zentrum für ambulante Onkologie GmbH, Tübingen, Germany.
  4. Universitätsklinikum Heidelberg, KiTZ, Hopp Children’s Cancer Center, Heidelberg, Germany.
  5. CeCaVa GmbH, Tübingen, Germany.
  6. Department of Dermatology, University Hospital Tübingen, Tübingen, Germany.
  7. Department für Radiologie, Universitätsklinikum Tübingen, Tübingen, Germany.
  8. Nuklearmedizin und Klinische Molekulare Bildgebung, Universitätsklinikum Tübingen, Tübingen, Germany.
  9. Provenance Precision Medicine Foundation, Wilmette, IL, USA.
  10. PHM, Los Angeles, CA, USA.
  11. Department of Hematology and Oncology, Cancer Center Heilbronn-Franken, SLK Kliniken GmbH, Heilbronn, Germany.
  12. Klinikum Stuttgart, Stuttgart, Germany.
  13. Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel Aviv, Israel.
  14. Vanderbilt University Medical Center, Nashville, TN, USA.
  15. Clínica Universidad de Navarra, Madrid, Spain.
  16. Jewish Theological Seminary-University of Jewish Studies (OR-ZSE), Budapest, Hungary.
  17. Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.
  18. Tom Baker Cancer Centre, Calgary, AB, Canada.
  19. Universitätsklinikum Essen, Essen, Germany.
  20. Angiogenesis Foundation, Cambridge, MA, USA.
  21. Harvard Medical School Dermatology, Boston, MA, USA.
  22. NHS London, London, UK.
  23. Brain and Spine Tumor Center, NYU Langone Health’s Perlmutter Cancer Center, New York, NY, USA.
  24. Pacific Neuroscience Institute, Saint John’s Cancer Institute, Providence Saint John’s Health Center, Santa Monica, CA, USA.
  25. Cellworks Group Inc, South San Francisco, CA, USA.
  26. Personalized Cancer Medicine, PLLC, Santa Monica, CA, USA.
  27. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.
  28. Preston Robert Tisch Brain Tumor Centre, Duke University, Durham, NC, USA.
  29. Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  30. Department of Neurology, University of Minnesota Health, Minneapolis, MN, USA.
  31. Columbia University Medical Center, New York, NY, USA.
  32. BAG für Pathologie und Molekularpathologie Stuttgart, Molekularpathologie Baden-Württemberg GbR, Stuttgart, Germany.
  33. Klinikum Darmstadt GmbH, Darmstadt, Germany.
  34. University Hospital Tübingen, Internal Medicine VIII, Tübingen, Germany.
  35. Division of Clinical Neurooncology, Department of Neurology, Universitätsklinikum Essen Klinik für Neurologie, Essen, Germany.
  36. Zentrum für Humangenetik Tübingen, Tübingen, Germany. Saskia.Biskup@humangenetik-tuebingen.de.
  37. CeGaT GmbH, Tübingen, Germany. Saskia.Biskup@humangenetik-tuebingen.de.