Neukirch and Uhrig-Schmidt et al. showed that a VLP approach using CD8 epitopes linked to the capsid protein was effective for tumor prevention and treatment. The capsid provided essential MHC-II epitopes that licensed CD4+ T cells to support CD8+ T cells. Synthetic peptide vaccination containing CD8 and CD4 epitopes demonstrated that physical linkage was not required, and that the CD4 epitope needed not be tumor specific. This was true in both preventive and therapeutic cancer vaccine settings. Retrospective analysis of personalized vaccine-treated patients showed post-vaccine immune responses only in patients harboring MHC-II epitopes.
Contributed by Shishir Pant
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.
Author Info: (1) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (2) Clinical Cooperation Unit "Applied T
Author Info: (1) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (2) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (3) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (4) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), 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. (6) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (7) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (8) GMP and T Cell Therapy Group, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, Heidelberg, Germany. (9) Clinical Cooperation Unit "Applied Tumor Immunity", German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, Heidelberg, Germany. (10) Department of Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 460, Heidelberg, Germany. (11) 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. (12) 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.
