Targeting mutated plus germline epitopes confers pre-clinical efficacy of an instantly formulated cancer nano-vaccine
Mohsen, Mona O.
Gomes, Ariane C.
Kundig, Thomas M.
Speiser, Daniel E.
Bachmann, Martin F.
Date of Issue2019
School of Biological Sciences
Molecular Genetics and Cell Biology
Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are sufficient, and whether the addition of germline antigens would enhance the therapeutic efficacy. We developed and used a personalized cancer nano-vaccine platform based on virus-like particles loaded with toll-like receptor ligands. We generated three sets of multi-target vaccines (MTV) to immunize against the aggressive B16F10 murine melanoma: one set based on germline epitopes (GL-MTV) identified by immunopeptidomics, another set based on mutated epitopes (Mutated-MTV) predicted by whole exome sequencing and a last set combines both germline and mutated epitopes (Mix-MTV). Our results demonstrate that both germline and mutated epitopes induced protection but the best therapeutic effect was achieved with the combination of both. Our platform is based on Cu-free click chemistry used for peptide-VLP coupling, thus enabling bedside production of a personalized cancer vaccine, ready for clinical translation.
Frontiers in Immunology
© 2019 Mohsen, Vogel, Riether, Muller, Salatino, Ternette, Gomes, Cabral-Miranda, El-Turabi, Ruedl, Kundig, Dermime, Knuth, Speiser and Bachmann. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.