RIG-I-based immunotherapy enhances survival in preclinical AML models and sensitizes AML cells to checkpoint blockade.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
Antibodies, Neutralizing
/ pharmacology
B7-H1 Antigen
/ antagonists & inhibitors
CD4-Positive T-Lymphocytes
/ drug effects
CD8-Positive T-Lymphocytes
/ drug effects
DEAD Box Protein 58
/ genetics
Disease Models, Animal
Drug Evaluation, Preclinical
Gene Expression Regulation
Heterografts
Humans
Immunologic Memory
/ drug effects
Immunotherapy
/ methods
Interferons
/ genetics
Isografts
Leukemia, Myeloid, Acute
/ genetics
Mice
RNA, Double-Stranded
/ pharmacology
Receptors, Virus
/ agonists
Remission Induction
Signal Transduction
Survival Analysis
Treatment Outcome
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
12
04
2019
accepted:
03
11
2019
revised:
14
10
2019
pubmed:
20
11
2019
medline:
26
8
2020
entrez:
20
11
2019
Statut:
ppublish
Résumé
Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic immune receptor sensing viral RNA. It triggers the release of type I interferons (IFN) and proinflammatory cytokines inducing an adaptive cellular immune response. We investigated the therapeutic potential of systemic RIG-I activation by short 5'-triphosphate-modified RNA (ppp-RNA) for the treatment of acute myeloid leukemia (AML) in the syngeneic murine C1498 AML tumor model. ppp-RNA treatment significantly reduced tumor burden, delayed disease onset and led to complete remission including immunological memory formation in a substantial proportion of animals. Therapy-induced tumor rejection was dependent on CD4
Identifiants
pubmed: 31740809
doi: 10.1038/s41375-019-0639-x
pii: 10.1038/s41375-019-0639-x
pmc: PMC7214254
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antibodies, Neutralizing
0
B7-H1 Antigen
0
Cd274 protein, mouse
0
IPS-1 protein, mouse
0
RNA, Double-Stranded
0
Receptors, Virus
0
Interferons
9008-11-1
Ddx58 protein, mouse
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1017-1026Références
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