TY  - JOUR
AU  - Neukirch, Lasse
AU  - Uhrig-Schmidt, Silke
AU  - von Werthern, Katharina
AU  - Tuch, Alexandra
AU  - Kraske, Joscha A
AU  - Lyu, Yanhong
AU  - Lenoir, Bénédicte
AU  - Eichmüller, Stefan
AU  - Meyer, Marten
AU  - Zörnig, Inka
AU  - Jäger, Dirk
AU  - Schmidt, Patrick
TI  - Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles.
JO  - Molecular therapy
VL  - nn
SN  - 1525-0016
CY  - Amsterdam
PB  - Elsevier
M1  - DKFZ-2025-01472
SP  - nn
PY  - 2025
N1  - #EA:D120#LA:D210# / epub
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:40671675
DO  - DOI:10.1016/j.ymthe.2025.07.014
UR  - https://inrepo02.dkfz.de/record/303025
ER  -