TY - JOUR
T1 - An rna toolbox for cancer immunotherapy
AU - Pastor, Fernando
AU - Berraondo, Pedro
AU - Etxeberria, Iñaki
AU - Frederick, Josh
AU - Sahin, Ugur
AU - Gilboa, Eli
AU - Melero, Ignacio
N1 - Funding Information:
This work was supported by Worldwide Cancer Research grants 15–1146 and 15–1208, the Asociación Española Contra el Cáncer (AECC) Foundation under grant GCB15152947MELE, Red Temática de Investigación Cooperativa en Cáncer under grants RD12/0036/0040 and RD12/0036/0062, Fondo de Investigación Sanitaria-Fondo Europeo de Desarrollo Regional (FEDER) under grants PI14/01686, PI13/00207, PI16/00668 and PI17/00372, the H2020 PROCROP project under grant 635122, the Melanoma Research Alliance under grant 509510 and the Fundación Ramón Areces under grant CIVP18A3916. F.P. is supported by Ramón y Cajal (10699). P.B. is supported by a Miguel Servet II (CPII15/00004) contract from the Instituto de Salud Carlos III.
Publisher Copyright:
© 2018 Springer Nature Limited. All rights reserved.
PY - 2018/10/1
Y1 - 2018/10/1
N2 - | 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.
AB - | 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.
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U2 - 10.1038/nrd.2018.132
DO - 10.1038/nrd.2018.132
M3 - Review article
C2 - 30190565
AN - SCOPUS:85054305618
VL - 17
SP - 751
EP - 767
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
SN - 1474-1776
IS - 10
ER -