% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Hilf:142870,
      author       = {N. Hilf and S. Kuttruff-Coqui and K. Frenzel and V. Bukur
                      and S. Stevanović$^*$ and C. Gouttefangeas$^*$ and M.
                      Platten$^*$ and G. Tabatabai$^*$ and V. Dutoit and S. H. van
                      der Burg and P. Thor Straten and F. Martínez-Ricarte and B.
                      Ponsati and H. Okada and U. Lassen and A. Admon and C. H.
                      Ottensmeier and A. Ulges and S. Kreiter and A. von
                      Deimling$^*$ and M. Skardelly and D. Migliorini and J. R.
                      Kroep and M. Idorn and J. Rodon and J. Piró and H. S.
                      Poulsen and B. Shraibman and K. McCann and R. Mendrzyk and
                      M. Löwer and M. Stieglbauer and C. M. Britten and D.
                      Capper$^*$ and M. J. P. Welters and J. Sahuquillo and K.
                      Kiesel and E. Derhovanessian and E. Rusch and L. Bunse$^*$
                      and C. Song and S. Heesch and C. Wagner and A. Kemmer-Brück
                      and J. Ludwig and J. C. Castle and O. Schoor and A. D.
                      Tadmor and E. Green$^*$ and J. Fritsche and M. Meyer and N.
                      Pawlowski and S. Dorner and F. Hoffgaard and B. Rössler and
                      D. Maurer and T. Weinschenk and C. Reinhardt and C. Huber
                      and H.-G. Rammensee$^*$ and H. Singh-Jasuja and U. Sahin and
                      P.-Y. Dietrich and W. Wick$^*$},
      title        = {{A}ctively personalized vaccination trial for newly
                      diagnosed glioblastoma.},
      journal      = {Nature},
      volume       = {565},
      number       = {7738},
      issn         = {1476-4687},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group52462},
      reportid     = {DKFZ-2019-00500},
      pages        = {240 - 245},
      year         = {2019},
      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.},
      cin          = {L801 / D170 / B300 / B320 / L101 / L501},
      ddc          = {500},
      cid          = {I:(DE-He78)L801-20160331 / I:(DE-He78)D170-20160331 /
                      I:(DE-He78)B300-20160331 / I:(DE-He78)B320-20160331 /
                      I:(DE-He78)L101-20160331 / I:(DE-He78)L501-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:30568303},
      doi          = {10.1038/s41586-018-0810-y},
      url          = {https://inrepo02.dkfz.de/record/142870},
}