An RNA toolbox for cancer immunotherapy
Pastor F (1), Berraondo P (2), Etxeberria I (2), Frederick J (3), Sahin U (4), Gilboa E (5), Melero I (2).
(1) Molecular Therapeutics Program, Center for Applied Medical Research, CIMA and IDISNA, Pamplona, Spain.
(2) Immunology and Immunotherapy Program, Center for Applied Medical Research, CIMA, Clinica Universidad de Navarra, IDISNA and CIBERONC, Pamplona, Spain.
(3) Moderna Therapeutics, Cambridge, MA, USA.
(4) Biopharmaceutical New Technologies (BioNTech) Corporation and TRON-Translational Oncology at the University Medical Center of Johannes Gutenberg University GmbH, Mainz, Germany.
(5) Department of Microbiology and Immunology, Dodson Interdisciplinary Immunotherapy Institute, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA.
Cancer immunotherapy has revolutionized oncology practice. However, current protein and cell therapy tools used in cancer immunotherapy are far from perfect, and there is room for improvement regarding their efficacy and safety. RNA-based structures have diverse functions, ranging from gene expression and gene regulation to pro-inflammatory effects and the ability to specifically bind different molecules.
These functions make them versatile tools that may advance cancer vaccines and immunomodulation, surpassing existing approaches. These technologies should not be considered as competitors of current immunotherapies but as partners in synergistic combinations and as a clear opportunity to reach more efficient and personalized results.
RNA and RNA derivatives can be exploited therapeutically as a platform to encode protein sequences, provide innate pro-inflammatory signals to the immune system (such as those denoting viral infection), control the expression of other RNAs (including key immunosuppressive factors) post-transcriptionally and conform structural scaffoldings binding proteins that control immune cells by modifying their function.
Nascent RNA immunotherapeutics include RNA vaccines encoding cancer neoantigens, mRNAs encoding immunomodulatory factors, viral RNA analogues, interference RNAs and protein-binding RNA aptamers. These approaches are already in early clinical development with promising safety and efficacy results.
CITATION Nat Rev Drug Discov. 2018 Oct;17(10):751-767. doi: 10.1038/nrd.2018.132