(1) Latzer P (2) Zelba H (3) Battke F (4) Reinhardt A (5) Shao B (6) Bartsch O (7) Rabsteyn A (8) Harter J (9) Schulze M (10) Okech T (11) Golf A (12) Kyzirakos-Feger C (13) Kayser S (14) Pieper N (15) Feldhahn M (16) WŸnsche J (17) Seitz C (18) Hadaschik D (19) Garbe C (20) Hauser TK (21) la Fougre C (22) Biskup D (23) Brooke D (24) Parker D (25) Martens UM (26) Illerhaus G (27) Blumenthal DT (28) Merrell R (29) Lorenzo LS (30) HidvŽgi M (31) de Robles P (32) Kebir S (33) Li WW (34) Li VW (35) Williams M (36) Miller AM (37) Kesari S (38) Castro M (39) Desjardins A (40) Ashley DM (41) Friedman HS (42) Wen PY (43) Neil EC (44) Iwamoto FM (45) Sipos B (46) Geletneky K (47) Zender L (48) Glas M (49) Reardon DA (50) Biskup S

Nature communications

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.

Author Info: (1) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (2) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (3) CeGaT GmbH, TŸbingen, Germany. (4) Zentrum fŸr Humangenetik

Author Info: (1) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (2) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (3) CeGaT GmbH, TŸbingen, Germany. (4) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (5) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (6) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (7) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (8) CeGaT GmbH, TŸbingen, Germany. (9) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (10) MVZ Zentrum fŸr ambulante Onkologie GmbH, TŸbingen, Germany. (11) MVZ Zentrum fŸr ambulante Onkologie GmbH, TŸbingen, Germany. (12) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (13) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (14) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. (15) CeGaT GmbH, TŸbingen, Germany. (16) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. MVZ Zentrum fŸr ambulante Onkologie GmbH, TŸbingen, Germany. (17) UniversitŠtsklinikum Heidelberg, KiTZ, Hopp Children's Cancer Center, Heidelberg, Germany. (18) CeCaVa GmbH, TŸbingen, Germany. (19) Department of Dermatology, University Hospital TŸbingen, TŸbingen, Germany. (20) Department fŸr Radiologie, UniversitŠtsklinikum TŸbingen, TŸbingen, Germany. (21) Nuklearmedizin und Klinische Molekulare Bildgebung, UniversitŠtsklinikum TŸbingen, TŸbingen, Germany. (22) CeGaT GmbH, TŸbingen, Germany. (23) Provenance Precision Medicine Foundation, Wilmette, IL, USA. (24) PHM, Los Angeles, CA, USA. (25) Department of Hematology and Oncology, Cancer Center Heilbronn-Franken, SLK Kliniken GmbH, Heilbronn, Germany. (26) Klinikum Stuttgart, Stuttgart, Germany. (27) Tel-Aviv Sourasky Medical Center, Tel-Aviv University, Tel Aviv, Israel. (28) Vanderbilt University Medical Center, Nashville, TN, USA. (29) Cl’nica Universidad de Navarra, Madrid, Spain. (30) Jewish Theological Seminary-University of Jewish Studies (OR-ZSE), Budapest, Hungary. (31) Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. Tom Baker Cancer Centre, Calgary, AB, Canada. (32) UniversitŠtsklinikum Essen, Essen, Germany. (33) Angiogenesis Foundation, Cambridge, MA, USA. (34) Angiogenesis Foundation, Cambridge, MA, USA. Harvard Medical School Dermatology, Boston, MA, USA. (35) NHS London, London, UK. (36) Brain and Spine Tumor Center, NYU Langone Health's Perlmutter Cancer Center, New York, NY, USA. (37) Pacific Neuroscience Institute, Saint John's Cancer Institute, Providence Saint John's Health Center, Santa Monica, CA, USA. (38) Cellworks Group Inc, South San Francisco, CA, USA. Personalized Cancer Medicine, PLLC, Santa Monica, CA, USA. (39) Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (40) Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. Preston Robert Tisch Brain Tumor Centre, Duke University, Durham, NC, USA. (41) Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (42) Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. (43) Department of Neurology, University of Minnesota Health, Minneapolis, MN, USA. (44) Columbia University Medical Center, New York, NY, USA. (45) BAG fŸr Pathologie und Molekularpathologie Stuttgart, Molekularpathologie Baden-WŸrttemberg GbR, Stuttgart, Germany. (46) Klinikum Darmstadt GmbH, Darmstadt, Germany. (47) University Hospital TŸbingen, Internal Medicine VIII, TŸbingen, Germany. (48) Division of Clinical Neurooncology, Department of Neurology, UniversitŠtsklinikum Essen Klinik fŸr Neurologie, Essen, Germany. (49) Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. (50) Zentrum fŸr Humangenetik TŸbingen, TŸbingen, Germany. Saskia.Biskup@humangenetik-tuebingen.de. CeGaT GmbH, TŸbingen, Germany. Saskia.Biskup@humangenetik-tuebingen.de.

Citation: Nat Commun 2024 Aug 11 15:6870 Epub08/11/2024

Link to PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/39127809

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