Journal Article

DKFZ-2019-00500

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Actively personalized vaccination trial for newly diagnosed glioblastoma.

Hilf, N. ; Kuttruff-Coqui, S. ; Frenzel, K. ; Bukur, V. ; Stevanović, S.DKFZ* ; Gouttefangeas, C.DKFZ* ; Platten, M.DKFZ* ; Tabatabai, G.DKFZ* ; Dutoit, V. ; van der Burg, S. H. ; Thor Straten, P. ; Martínez-Ricarte, F. ; Ponsati, B. ; Okada, H. ; Lassen, U. ; Admon, A. ; Ottensmeier, C. H. ; Ulges, A. ; Kreiter, S. ; von Deimling, A.DKFZ* ; Skardelly, M. ; Migliorini, D. ; Kroep, J. R. ; Idorn, M. ; Rodon, J. ; Piró, J. ; Poulsen, H. S. ; Shraibman, B. ; McCann, K. ; Mendrzyk, R. ; Löwer, M. ; Stieglbauer, M. ; Britten, C. M. ; Capper, D.DKFZ* ; Welters, M. J. P. ; Sahuquillo, J. ; Kiesel, K. ; Derhovanessian, E. ; Rusch, E. ; Bunse, L.DKFZ* ; Song, C. ; Heesch, S. ; Wagner, C. ; Kemmer-Brück, A. ; Ludwig, J. ; Castle, J. C. ; Schoor, O. ; Tadmor, A. D. ; Green, E.DKFZ* ; Fritsche, J. ; Meyer, M. ; Pawlowski, N. ; Dorner, S. ; Hoffgaard, F. ; Rössler, B. ; Maurer, D. ; Weinschenk, T. ; Reinhardt, C. ; Huber, C. ; Rammensee, H.-G.DKFZ* ; Singh-Jasuja, H. ; Sahin, U. ; Dietrich, P.-Y. ; Wick, W. (Last author)DKFZ*

2019
Nature Publ. Group52462 London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41586-018-0810-y

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.

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Contributing Institute(s):

1. DKTK Tübingen (L801)
2. KKE Neuroimmunologie und Hirntumorimmunologie (D170)
3. KKE Neuropathologie (B300)
4. KKE Neuroonkologie (B320)
5. DKTK Heidelberg (L101)
6. DKTK Frankfurt (L501)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2019

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