Mutated as well as germ-line epitopes contribute to preclinical efficacy of virus-like particles based cancer vaccines
Mohsen MO., Muller J., Ternette N., Zha L., Riether C., Luethi U., Ruckstuhl C., Roestti E., Gomes A., El-Turabi A., de Miranda GC., Vogel M., Dermim S., Kundig T., Knuth A., Speiser D., Bachmann M.
Personalized cancer vaccines combined with check-point inhibitors hold promise for future therapies for cancer. It remains, however, unclear whether optimal epitopes for vaccination should be mutated or whether germ-line epitopes may also have some merits. In addition, it has remained difficult to induce strong cytotoxic T cell responses in vivo in the absence of viral vectors. Here we develop a personalized cancer vaccine platform based on virus-like particles (VLPs) loaded with toll-like receptor ligands and generate three sets of multi-target vaccines: One set based on germ-line epitopes (GL-MTV) identified by immune-peptidomics, one set based on mutated epitopes (Mutated- MTV) and one set that combines the two (Mix-MTV). Vaccine efficacy was tested in mice transplanted with B16F10 melanoma tumors to have a realistic, well vascularized and in situ established cancer model. Our results demonstrate that both germ-line and mutated neo-epitopes induced partial protection but best protection was achieved with a cocktail containing both types of peptides. Thus, both germ-line and neo-epitopes are valuable targets and VLP-based vaccines displaying both types of epitopes may confer optimal protection.