Exploiting the Mutanome for Personalized Cancer Immunotherapy
Ugur Sahin, Sebastian Kreiter, John Castle, Martin Löwer, Cedrik Britten and Özlem Türeci
from: Advanced Vaccine Research Methods for the Decade of Vaccines (Edited by: Fabio Bagnoli and Rino Rappuoli). Caister Academic Press, U.K. (2015) Pages: 263-270.
Cancer mutations conceptually represent ideal targets for cancer immunotherapy as they combine a favorable safety due to the lack of their expression in healthy tissues and capability of supreme immunogenicity as they are not affected by central tolerance mechanisms. However, the systematic immunotherapeutic targeting of cancer mutations is hampered so far as 95% of the mutations in a tumor are unique to that single patient and only a small number of mutations are shared between patients. We have recently introduced a personalized immunotherapy approach targeting the spectrum of individual mutations by joining innovations from different technology fields. Next generation sequencing (NGS) is applied to enable the rapid identification of somatic mutations in individual tumors (the mutanome). Immunoinformatic tools are applied for prioritization of mutated epitopes that are predicted to be highly immunogenic and presented on MHC molecules. RNA-based vaccines encoding multiple mutations can be rapidly and affordably synthesized as custom GMP drug products. Integration of these cutting edge technologies into a clinically applicable process holds the promise of successful targeting of cancer heterogeneity by the multi-epitope approach read more ...