%0 Journal Article
%A Neukirch, Lasse
%A Uhrig-Schmidt, Silke
%A von Werthern, Katharina
%A Tuch, Alexandra
%A Kraske, Joscha A
%A Lyu, Yanhong
%A Lenoir, Bénédicte
%A Eichmüller, Stefan
%A Meyer, Marten
%A Zörnig, Inka
%A Jäger, Dirk
%A Schmidt, Patrick
%T Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles.
%J Molecular therapy
%V nn
%@ 1525-0016
%C Amsterdam
%I Elsevier
%M DKFZ-2025-01472
%P nn
%D 2025
%Z #EA:D120#LA:D210# / epub
%X Personalized treatment has become a realistic option for tumor patients, accelerated by significantly reduced sequencing costs of tumor genomes and advances in vaccine formulations. The druggability of cancer neo-antigens caused by individual mutations is centered in this effort. We here use an AAV-based VLP platform to compose a neo-antigen specific protein vaccine that is effective in a murine prevention and treatment setting. Furthermore, we show that CD4+ T cell responses that are provided by the AAV capsid are crucial for an effective murine melanoma treatment. To uncover the optimal composition of a peptide vaccine we de-linked MHC-II helper peptides from the capsid and formulated an efficient neo-antigen specific vaccine, which showed the independence of CD4+ T cell response from tumor sequences. The findings are supported by clinical data of neo-antigen vaccinated tumor patients. Our results punctuate on the significance of MHC-II epitopes for CD8+ T cell responses and suggest a future use of AAVLPs as neo-epitope vaccines in personalized cancer treatments.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40671675
%R 10.1016/j.ymthe.2025.07.014
%U https://inrepo02.dkfz.de/record/303025