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000142870 037__ $$aDKFZ-2019-00500
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000142870 1001_ $$aHilf, Norbert$$b0
000142870 245__ $$aActively personalized vaccination trial for newly diagnosed glioblastoma.
000142870 260__ $$aLondon [u.a.]$$bNature Publ. Group52462$$c2019
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000142870 520__ $$aPatients 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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000142870 7001_ $$aKuttruff-Coqui, Sabrina$$b1
000142870 7001_ $$aFrenzel, Katrin$$b2
000142870 7001_ $$aBukur, Valesca$$b3
000142870 7001_ $$0P:(DE-HGF)0$$aStevanović, Stefan$$b4
000142870 7001_ $$0P:(DE-HGF)0$$aGouttefangeas, Cécile$$b5
000142870 7001_ $$0P:(DE-He78)5ef8651b0f857b9c640aa5b1498c43b5$$aPlatten, Michael$$b6$$udkfz
000142870 7001_ $$0P:(DE-HGF)0$$aTabatabai, Ghazaleh$$b7
000142870 7001_ $$aDutoit, Valerie$$b8
000142870 7001_ $$avan der Burg, Sjoerd H$$b9
000142870 7001_ $$aThor Straten, Per$$b10
000142870 7001_ $$aMartínez-Ricarte, Francisco$$b11
000142870 7001_ $$aPonsati, Berta$$b12
000142870 7001_ $$aOkada, Hideho$$b13
000142870 7001_ $$aLassen, Ulrik$$b14
000142870 7001_ $$aAdmon, Arie$$b15
000142870 7001_ $$aOttensmeier, Christian H$$b16
000142870 7001_ $$aUlges, Alexander$$b17
000142870 7001_ $$aKreiter, Sebastian$$b18
000142870 7001_ $$0P:(DE-He78)a8a10626a848d31e70cfd96a133cc144$$avon Deimling, Andreas$$b19$$udkfz
000142870 7001_ $$aSkardelly, Marco$$b20
000142870 7001_ $$aMigliorini, Denis$$b21
000142870 7001_ $$aKroep, Judith R$$b22
000142870 7001_ $$aIdorn, Manja$$b23
000142870 7001_ $$aRodon, Jordi$$b24
000142870 7001_ $$aPiró, Jordi$$b25
000142870 7001_ $$aPoulsen, Hans S$$b26
000142870 7001_ $$aShraibman, Bracha$$b27
000142870 7001_ $$aMcCann, Katy$$b28
000142870 7001_ $$aMendrzyk, Regina$$b29
000142870 7001_ $$aLöwer, Martin$$b30
000142870 7001_ $$aStieglbauer, Monika$$b31
000142870 7001_ $$aBritten, Cedrik M$$b32
000142870 7001_ $$0P:(DE-He78)51bf9ae9cb5771b30c483e5597ef606c$$aCapper, David$$b33$$udkfz
000142870 7001_ $$aWelters, Marij J P$$b34
000142870 7001_ $$aSahuquillo, Juan$$b35
000142870 7001_ $$aKiesel, Katharina$$b36
000142870 7001_ $$aDerhovanessian, Evelyna$$b37
000142870 7001_ $$aRusch, Elisa$$b38
000142870 7001_ $$0P:(DE-He78)e579130c57e8c686ed1c2dedfa595985$$aBunse, Lukas$$b39$$udkfz
000142870 7001_ $$aSong, Colette$$b40
000142870 7001_ $$aHeesch, Sandra$$b41
000142870 7001_ $$aWagner, Claudia$$b42
000142870 7001_ $$aKemmer-Brück, Alexandra$$b43
000142870 7001_ $$aLudwig, Jörg$$b44
000142870 7001_ $$aCastle, John C$$b45
000142870 7001_ $$aSchoor, Oliver$$b46
000142870 7001_ $$aTadmor, Arbel D$$b47
000142870 7001_ $$0P:(DE-He78)9b97ca569bcb00dfda69382bc7261700$$aGreen, Edward$$b48$$udkfz
000142870 7001_ $$aFritsche, Jens$$b49
000142870 7001_ $$aMeyer, Miriam$$b50
000142870 7001_ $$aPawlowski, Nina$$b51
000142870 7001_ $$aDorner, Sonja$$b52
000142870 7001_ $$aHoffgaard, Franziska$$b53
000142870 7001_ $$aRössler, Bernhard$$b54
000142870 7001_ $$aMaurer, Dominik$$b55
000142870 7001_ $$aWeinschenk, Toni$$b56
000142870 7001_ $$aReinhardt, Carsten$$b57
000142870 7001_ $$aHuber, Christoph$$b58
000142870 7001_ $$0P:(DE-He78)58a4f09f3edfdce451d520a5be7979fc$$aRammensee, Hans-Georg$$b59$$udkfz
000142870 7001_ $$aSingh-Jasuja, Harpreet$$b60
000142870 7001_ $$aSahin, Ugur$$b61
000142870 7001_ $$aDietrich, Pierre-Yves$$b62
000142870 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b63$$eLast author$$udkfz
000142870 773__ $$0PERI:(DE-600)1413423-8$$a10.1038/s41586-018-0810-y$$gVol. 565, no. 7738, p. 240 - 245$$n7738$$p240 - 245$$tNature <London>$$v565$$x1476-4687$$y2019
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