PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Helms, M.W.* ; Jahn-Hofmann, K.* ; Gnerlich, F.* ; Metz-Weidmann, C.* ; Braun, M.* ; Dietert, G.* ; Scherer, P.* ; Grandien, K.* ; Theilhaber, J.* ; Cao, H.* ; Wagenaar, T.R.* ; Schnurr, M.M.* ; Endres, S. ; Wiederschain, D.* ; Scheidler, S.* ; Rothenfußer, S. ; Brunner, B.* ; König, L.M.*

Utility of the RIG-I agonist triphosphate RNA for melanoma therapy.

Mol. Cancer Ther. 18, 2343-2356 (2019)
Postprint DOI
Open Access Green
The pattern recognition receptor RIG-I plays an important role in the recognition of nonself RNA and antiviral immunity. RIG-I's natural ligand, triphosphate RNA (ppp-RNA), is proposed to be a valuable addition to the growing arsenal of cancer immunotherapy treatment options. In this study, we present comprehensive data validating the concept and utility of treatment with synthetic RIG-I agonist ppp-RNA for the therapy of human cancer, with melanoma as potential entry indication amenable to intratumoral treatment. Using mRNA expression data of human tumors, we demonstrate that RIG-I expression is closely correlated to cellular and cytokine immune activation in a wide variety of tumor types. Furthermore, we confirm susceptibility of cancer cells to ppp-RNA treatment in different cellular models of human melanoma, revealing unexpected heterogeneity between cell lines in their susceptibility to RNA agonist features, including sequence, secondary structures, and presence of triphosphate. Cellular responses to RNA treatment (induction of type I IFN, FasK, MHC-I, and cytotoxicity) were demonstrated to be RIG-I dependent using KO cells. Following ppp-RNA treatment of a mouse melanoma model, we observed significant local and systemic antitumor effects and survival benefits. These were associated with type I IFN response, tumor cell apoptosis, and innate and adaptive immune cell activation. For the first time, we demonstrate systemic presence of tumor antigen-specific Cris following treatment with RIG-I agonists. Despite potential challenges in the generation and formulation of potent RIG-I agonists, ppp-RNA or analogues thereof have the potential to play an important role for cancer treatment in the next wave of immunotherapy.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
4.856
1.192
5
7
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Double-stranded-rna; 5'-triphosphate Rna; Checkpoint Blockade; Interferon-alpha; Cancer-therapy; Cutting Edge; T-cells; Activation; Il-10; Interleukin-10
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 1535-7163
e-ISSN 1538-8514
Zeitschrift Molecular Cancer Therapeutics
Quellenangaben Band: 18, Heft: 12, Seiten: 2343-2356 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
Begutachtungsstatus Peer reviewed
Institut(e) Unit for Clinical Pharmacology (KKG-EKLiP)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-522100-001
Förderungen Else Kroner-Fresenius-Stiftung
international doctoral program "i-Target: Immunotargeting of cancer" - the Elite Network of Bavaria
Deutsche Forschungsgemeinschaft
DOI 10.1158/1535-7163.MCT-18-1262
WOS ID WOS:000596730500014
WOS ID WOS:000500955700014
Scopus ID 85075957067
Erfassungsdatum 2019-12-23
[➜Korrektur melden]