2. Academic Validation
  3. Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles

Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles

  • Mol Ther. 2025 Jul 16:S1525-0016(25)00549-0. doi: 10.1016/j.ymthe.2025.07.014.
Lasse Neukirch 1,  Silke Uhrig-Schmidt 1,  Katharina von Werthern 1,  Alexandra Tuch 1,  Joscha A Kraske 2,  Yanhong Lyu 1,  Benedicte Lenoir 1,  Stefan B Eichmüller 3,  Marten Meyer 1,  Inka Zörnig 2,  Dirk Jäger 4,  Patrick Schmidt 5
Affiliations

Affiliations

  • 1 Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany.
  • 2 Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, Heidelberg, Germany.
  • 3 GMP and T Cell Therapy Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany.
  • 4 Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany; Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, Heidelberg, Germany.
  • 5 Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, Heidelberg, Germany; GMP and T Cell Therapy Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany. Electronic address: patrick.schmidt@nct-heidelberg.de.
PMID: 40671675 DOI: 10.1016/j.ymthe.2025.07.014
Abstract

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 adeno-associated virus (AAV)-based virus-like particle (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 effective murine melanoma treatment. To uncover the optimal composition of a peptide vaccine we de-linked major histocompatibility complex (MHC) class 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 class II epitopes for CD8+ T cell responses and suggest a future use of AAVLPs as neo-epitope vaccines in personalized Cancer treatments.

Keywords

AAVLP; CD4 licensing; immunotherapy; neo-antigen; vaccine.

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