TY  - JOUR
AU  - Hilf, Norbert
AU  - Kuttruff-Coqui, Sabrina
AU  - Frenzel, Katrin
AU  - Bukur, Valesca
AU  - Stevanović, Stefan
AU  - Gouttefangeas, Cécile
AU  - Platten, Michael
AU  - Tabatabai, Ghazaleh
AU  - Dutoit, Valerie
AU  - van der Burg, Sjoerd H
AU  - Thor Straten, Per
AU  - Martínez-Ricarte, Francisco
AU  - Ponsati, Berta
AU  - Okada, Hideho
AU  - Lassen, Ulrik
AU  - Admon, Arie
AU  - Ottensmeier, Christian H
AU  - Ulges, Alexander
AU  - Kreiter, Sebastian
AU  - von Deimling, Andreas
AU  - Skardelly, Marco
AU  - Migliorini, Denis
AU  - Kroep, Judith R
AU  - Idorn, Manja
AU  - Rodon, Jordi
AU  - Piró, Jordi
AU  - Poulsen, Hans S
AU  - Shraibman, Bracha
AU  - McCann, Katy
AU  - Mendrzyk, Regina
AU  - Löwer, Martin
AU  - Stieglbauer, Monika
AU  - Britten, Cedrik M
AU  - Capper, David
AU  - Welters, Marij J P
AU  - Sahuquillo, Juan
AU  - Kiesel, Katharina
AU  - Derhovanessian, Evelyna
AU  - Rusch, Elisa
AU  - Bunse, Lukas
AU  - Song, Colette
AU  - Heesch, Sandra
AU  - Wagner, Claudia
AU  - Kemmer-Brück, Alexandra
AU  - Ludwig, Jörg
AU  - Castle, John C
AU  - Schoor, Oliver
AU  - Tadmor, Arbel D
AU  - Green, Edward
AU  - Fritsche, Jens
AU  - Meyer, Miriam
AU  - Pawlowski, Nina
AU  - Dorner, Sonja
AU  - Hoffgaard, Franziska
AU  - Rössler, Bernhard
AU  - Maurer, Dominik
AU  - Weinschenk, Toni
AU  - Reinhardt, Carsten
AU  - Huber, Christoph
AU  - Rammensee, Hans-Georg
AU  - Singh-Jasuja, Harpreet
AU  - Sahin, Ugur
AU  - Dietrich, Pierre-Yves
AU  - Wick, Wolfgang
TI  - Actively personalized vaccination trial for newly diagnosed glioblastoma.
JO  - Nature 
VL  - 565
IS  - 7738
SN  - 1476-4687
CY  - London [u.a.]
PB  - Nature Publ. Group52462
M1  - DKFZ-2019-00500
SP  - 240 - 245
PY  - 2019
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:30568303
DO  - DOI:10.1038/s41586-018-0810-y
UR  - https://inrepo02.dkfz.de/record/142870
ER  -