ATRTPepVac

AT/RT tumors of the CNS are highly aggressive tumors especially in small children which respond to chemo- and radiotherapy but often relapse. Immunotherapy could be a useful and targeted strategy to improve long-term remission control. Results from other cancer entities have shown that the immunogenic target structures of tumors are highly individual and vary with the extent of genetic alterations. AT/RT are known for their very low number of mutations per tumor, but no data on the AT/RT ligandome are available so far. In this project, we collected samples from 23 AT/RT tumors so far and are currently analyzing the HLA-ligandome of these tissues. In the mass-spectrometric analyses, a total of 54 MHC class I and 151 MHC class II tumor-exclusive ligands could be identified. Analyses regarding immunogenicity of these candidate peptides are under way. Furthermore, we compared MHC binding affinity and immunogenicity of these tumor-specific peptides with identifiable neoantigens from the same tumors. Ligandome peptides showed superior MHC-binding affinities compared to theoretically predicted neoepitopes, confirming their suitability for immunotherapy.

Natural and cryptic peptides dominate the immunopeptidome of atypical teratoid rhabdoid tumors.
Ana Marcu, Andreas Schlosser, Anne Keupp, Nico Trautwein, Pascal Johann, Matthias Wölfl, Johanna Lager, Camelia Maria Monoranu, Juliane S Walz, Lisa M Henkel, Jürgen Krauß, Martin Ebinger, Martin Schuhmann, Ulrich Wilhelm Thomale, Torsten Pietsch, Erdwine Klinker, Paul G Schlegel, Florian Oyen, Yair Reisner, Hans-Georg Rammensee, Matthias Eyrich.
J Immunother Cancer, 2021 Oct;9(10):e003404.
PMID: 34599019 DOI: 10.1136/jitc-2021-003404