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Nature. 2019 Jan;565(7738):240-245. doi: 10.1038/s41586-018-0810-y. Epub 2018 Dec 19.

Actively personalized vaccination trial for newly diagnosed glioblastoma.

Author information

1
Immatics Biotechnologies GmbH, Tübingen, Germany.
2
BioNTech AG, Mainz, Germany.
3
Eberhard Karls Universität Tübingen, Tübingen, Germany.
4
German Cancer Consortium (DKTK), German Cancer Research Center Partner Site Tübingen, Tübingen, Germany.
5
CIMT/CIP - Association for Cancer Immunotherapy, working group Cancer Immunoguiding Program, Mainz, Germany.
6
University Hospital Heidelberg, Heidelberg, Germany.
7
German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany.
8
Medical Faculty Mannheim, Mannheim, Germany.
9
University Hospital Tübingen, Tübingen, Germany.
10
Geneva University Hospital, Geneva, Switzerland.
11
Leiden University Medical Center, Leiden, The Netherlands.
12
Center for Cancer Immune Therapy (CCIT), Department of Hematology, University Hospital Herlev, Herlev, Denmark.
13
Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
14
Vall d'Hebron University Hospital, Barcelona, Spain.
15
BCN Peptides SA, Barcelona, Spain.
16
University of California, San Francisco, San Francisco, CA, USA.
17
Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA.
18
Ringhospitalet, Copenhagen, Denmark.
19
Technion - Israel Institute of Technology, Haifa, Israel.
20
University of Southampton, Southampton, UK.
21
M. D. Anderson Cancer Center, University of Texas, Houston, TX, USA.
22
Oncology R&D, GlaxoSmithKline, Stevenage, UK.
23
Charité, University Medicine Berlin, Berlin, Germany.
24
Agenus Inc., Lexington, KY, USA.
25
TRON GmbH - Translational Oncology at the University Medical Center of Johannes Gutenberg University, Mainz, Germany.
26
University Hospital Heidelberg, Heidelberg, Germany. wolfgang.wick@med.uni-heidelberg.de.
27
German Cancer Consortium (DKTK), German Cancer Research Center, Heidelberg, Germany. wolfgang.wick@med.uni-heidelberg.de.

Abstract

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.

PMID:
30568303
DOI:
10.1038/s41586-018-0810-y

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