Translation of genomics-guided RNA-based personalised cancer vaccines: towards the bedside

Abstract

Cancer is a disease caused by DNA mutations. Cancer therapies targeting defined functional mutations have shown clinical benefit. However, as 95% of the mutations in a tumour are unique to that single patient and only a small number of mutations are shared between patients, the addressed medical need is modest. A rapidly determined patient-specific tumour mutation pattern combined with a flexible mutation-targeting drug platform could generate a mutation-targeting individualised therapy, which would benefit each single patient. Next-generation sequencing enables the rapid identification of somatic mutations in individual tumours (the mutanome). Immunoinformatics enables predictions of mutation immunogenicity. Mutation-targeting RNA-based vaccines can be rapidly and affordably synthesised as custom GMP drug products. Integration of these cutting-edge technologies into a clinically applicable process holds the promise of a disruptive innovation benefiting cancer patients. Here, we describe our translation of the individualised RNA-based cancer vaccine concept into clinic trials.

Figure 1

The individualised cancer vaccine concept. Mutations and gene expression are determined by NGS and bioinformatics. After identification of those mutations that have a likelihood of being immunogenic (T-cell-druggable mutanome), the blueprint for a unique, mutation-targeted vaccine is generated and the respective RNA-based vaccine is manufactured. In preclinical mouse proof-of-concept models, we have demonstrated that such vaccines activate mutation-specific T cells and mediate growth inhibition of established tumours.