Journal article
Actively personalized vaccination trial for newly diagnosed glioblastoma.
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Hilf N
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Kuttruff-Coqui S
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Frenzel K
BioNTech AG, Mainz, Germany.
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Bukur V
BioNTech AG, Mainz, Germany.
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Stevanović S
Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Gouttefangeas C
Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Platten M
University Hospital Heidelberg, Heidelberg, Germany.
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Tabatabai G
Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Dutoit V
Geneva University Hospital, Geneva, Switzerland.
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van der Burg SH
CIMT/CIP - Association for Cancer Immunotherapy, working group Cancer Immunoguiding Program, Mainz, Germany.
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Thor Straten P
CIMT/CIP - Association for Cancer Immunotherapy, working group Cancer Immunoguiding Program, Mainz, Germany.
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Martínez-Ricarte F
Vall d'Hebron University Hospital, Barcelona, Spain.
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Ponsati B
BCN Peptides SA, Barcelona, Spain.
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Okada H
University of California, San Francisco, San Francisco, CA, USA.
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Lassen U
Ringhospitalet, Copenhagen, Denmark.
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Admon A
Technion - Israel Institute of Technology, Haifa, Israel.
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Ottensmeier CH
University of Southampton, Southampton, UK.
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Ulges A
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Kreiter S
BioNTech AG, Mainz, Germany.
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von Deimling A
University Hospital Heidelberg, Heidelberg, Germany.
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Skardelly M
University Hospital Tübingen, Tübingen, Germany.
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Migliorini D
Geneva University Hospital, Geneva, Switzerland.
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Kroep JR
Leiden University Medical Center, Leiden, The Netherlands.
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Idorn M
Center for Cancer Immune Therapy (CCIT), Department of Hematology, University Hospital Herlev, Herlev, Denmark.
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Rodon J
Vall d'Hebron University Hospital, Barcelona, Spain.
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Piró J
BCN Peptides SA, Barcelona, Spain.
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Poulsen HS
Ringhospitalet, Copenhagen, Denmark.
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Shraibman B
Technion - Israel Institute of Technology, Haifa, Israel.
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McCann K
University of Southampton, Southampton, UK.
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Mendrzyk R
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Löwer M
BioNTech AG, Mainz, Germany.
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Stieglbauer M
Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Britten CM
BioNTech AG, Mainz, Germany.
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Capper D
University Hospital Heidelberg, Heidelberg, Germany.
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Welters MJP
CIMT/CIP - Association for Cancer Immunotherapy, working group Cancer Immunoguiding Program, Mainz, Germany.
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Sahuquillo J
Vall d'Hebron University Hospital, Barcelona, Spain.
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Kiesel K
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Derhovanessian E
BioNTech AG, Mainz, Germany.
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Rusch E
Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Bunse L
University Hospital Heidelberg, Heidelberg, Germany.
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Song C
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Heesch S
BioNTech AG, Mainz, Germany.
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Wagner C
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Kemmer-Brück A
BioNTech AG, Mainz, Germany.
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Ludwig J
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Castle JC
BioNTech AG, Mainz, Germany.
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Schoor O
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Tadmor AD
TRON GmbH - Translational Oncology at the University Medical Center of Johannes Gutenberg University, Mainz, Germany.
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Green E
German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany.
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Fritsche J
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Meyer M
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Pawlowski N
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Dorner S
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Hoffgaard F
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Rössler B
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Maurer D
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Weinschenk T
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Reinhardt C
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Huber C
BioNTech AG, Mainz, Germany.
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Rammensee HG
Eberhard Karls Universität Tübingen, Tübingen, Germany.
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Singh-Jasuja H
Immatics Biotechnologies GmbH, Tübingen, Germany.
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Sahin U
BioNTech AG, Mainz, Germany.
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Dietrich PY
Geneva University Hospital, Geneva, Switzerland.
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Wick W
University Hospital Heidelberg, Heidelberg, Germany. wolfgang.wick@med.uni-heidelberg.de.
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English
Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors1,2. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential3. There is limited intratumoural infiltration of immune cells4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations5. Exploitation of the full repertoire of tumour antigens-that is, both unmutated antigens and neoepitopes-may offer more effective immunotherapies, especially for tumours with a low mutational load. Here, in the phase I trial GAPVAC-101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma. Fifteen patients with glioblastomas positive for human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 were treated with a vaccine (APVAC1) derived from a premanufactured library of unmutated antigens followed by treatment with APVAC2, which preferentially targeted neoepitopes. Personalization was based on mutations and analyses of the transcriptomes and immunopeptidomes of the individual tumours. The GAPVAC approach was feasible and vaccines that had poly-ICLC (polyriboinosinic-polyribocytidylic acid-poly-L-lysine carboxymethylcellulose) and granulocyte-macrophage colony-stimulating factor as adjuvants displayed favourable safety and strong immunogenicity. Unmutated APVAC1 antigens elicited sustained responses of central memory CD8+ T cells. APVAC2 induced predominantly CD4+ T cell responses of T helper 1 type against predicted neoepitopes.
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Language
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Open access status
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green
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Identifiers
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Persistent URL
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https://sonar.ch/global/documents/232658
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