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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.
Despite new treatment options, prognosis for patients with glioblastoma (GBM) remains poor. Here the authors report the clinical course of patients with GBM treated with a personalized neoantigen-derived peptide vaccine treated within the scope of an individual healing attempt.
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1 Zentrum für Humangenetik Tübingen, Tübingen, Germany
2 CeGaT GmbH, Tübingen, Germany (GRID:grid.498061.2) (ISNI:0000 0004 6008 5552)
3 Zentrum für Humangenetik Tübingen, Tübingen, Germany (GRID:grid.498061.2)
4 MVZ Zentrum für ambulante Onkologie GmbH, Tübingen, Germany (GRID:grid.498061.2)
5 Zentrum für Humangenetik Tübingen, Tübingen, Germany (GRID:grid.498061.2); MVZ Zentrum für ambulante Onkologie GmbH, Tübingen, Germany (GRID:grid.498061.2)
6 KiTZ, Hopp Children’s Cancer Center, Universitätsklinikum Heidelberg, Heidelberg, Germany (GRID:grid.5253.1) (ISNI:0000 0001 0328 4908)
7 CeCaVa GmbH, Tübingen, Germany (GRID:grid.5253.1)
8 University Hospital Tübingen, Department of Dermatology, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249)
9 Universitätsklinikum Tübingen, Department für Radiologie, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249)
10 Universitätsklinikum Tübingen, Nuklearmedizin und Klinische Molekulare Bildgebung, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249)
11 Provenance Precision Medicine Foundation, Wilmette, USA (GRID:grid.498061.2)
12 PHM, Los Angeles, USA (GRID:grid.498061.2)
13 Cancer Center Heilbronn-Franken, SLK Kliniken GmbH, Department of Hematology and Oncology, Heilbronn, Germany (GRID:grid.492899.7) (ISNI:0000 0001 0142 7696)
14 Klinikum Stuttgart, Stuttgart, Germany (GRID:grid.419842.2) (ISNI:0000 0001 0341 9964)
15 Tel-Aviv University, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel (GRID:grid.12136.37) (ISNI:0000 0004 1937 0546)
16 Vanderbilt University Medical Center, Nashville, USA (GRID:grid.412807.8) (ISNI:0000 0004 1936 9916)
17 Clínica Universidad de Navarra, Madrid, Spain (GRID:grid.411730.0) (ISNI:0000 0001 2191 685X)
18 Jewish Theological Seminary—University of Jewish Studies (OR-ZSE), Budapest, Hungary (GRID:grid.447152.1) (ISNI:0000 0001 1940 8899)
19 University of Calgary, Department of Clinical Neurosciences, Calgary, Canada (GRID:grid.22072.35) (ISNI:0000 0004 1936 7697); Tom Baker Cancer Centre, Calgary, Canada (GRID:grid.413574.0) (ISNI:0000 0001 0693 8815)
20 Universitätsklinikum Essen, Essen, Germany (GRID:grid.410718.b) (ISNI:0000 0001 0262 7331)
21 Angiogenesis Foundation, Cambridge, USA (GRID:grid.430443.4)
22 Angiogenesis Foundation, Cambridge, USA (GRID:grid.430443.4); Harvard Medical School Dermatology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
23 NHS London, London, UK (GRID:grid.451052.7) (ISNI:0000 0004 0581 2008)
24 NYU Langone Health’s Perlmutter Cancer Center, Brain and Spine Tumor Center, New York, USA (GRID:grid.451052.7)
25 Providence Saint John’s Health Center, Pacific Neuroscience Institute, Saint John’s Cancer Institute, Santa Monica, USA (GRID:grid.416507.1) (ISNI:0000 0004 0450 0360)
26 Cellworks Group Inc, South San Francisco, USA (GRID:grid.519384.2) (ISNI:0000 0004 0408 642X); Personalized Cancer Medicine, PLLC, Santa Monica, USA (GRID:grid.519384.2)
27 Duke University Medical Center, Department of Neurosurgery, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216)
28 Duke University Medical Center, Department of Neurosurgery, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216); Duke University, Preston Robert Tisch Brain Tumor Centre, Durham, USA (GRID:grid.26009.3d) (ISNI:0000 0004 1936 7961)
29 Harvard Medical School, Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
30 University of Minnesota Health, Department of Neurology, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000 0004 1936 8657)
31 Columbia University Medical Center, New York, USA (GRID:grid.239585.0) (ISNI:0000 0001 2285 2675)
32 Molekularpathologie Baden-Württemberg GbR, BAG für Pathologie und Molekularpathologie Stuttgart, Stuttgart, Germany (GRID:grid.239585.0)
33 Klinikum Darmstadt GmbH, Darmstadt, Germany (GRID:grid.419810.5)
34 Internal Medicine VIII, University Hospital Tübingen, Tübingen, Germany (GRID:grid.411544.1) (ISNI:0000 0001 0196 8249)
35 Universitätsklinikum Essen Klinik für Neurologie, Division of Clinical Neurooncology, Department of Neurology, Essen, Germany (GRID:grid.410718.b) (ISNI:0000 0001 0262 7331)
36 Zentrum für Humangenetik Tübingen, Tübingen, Germany (GRID:grid.38142.3c); CeGaT GmbH, Tübingen, Germany (GRID:grid.498061.2) (ISNI:0000 0004 6008 5552)