Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses.
J Exp Med
; 216(12): 2854-2868, 2019 12 02.
Article
em En
| MEDLINE
| ID: mdl-31601678
ABSTRACT
Cytosolic nucleic acid-sensing pathways can be triggered to enhance immune response to cancer. In this study, we tested the antitumor activity of a unique RIG-I agonist, stem loop RNA (SLR) 14. In the immunogenic tumor models, we observed significant tumor growth delay and an extended survival in SLR14-treated mice. SLR14 also greatly improved antitumor efficacy of anti-PD1 antibody over single-agent treatment. SLR14 was mainly taken up by CD11b+ myeloid cells in the tumor microenvironment, and many genes associated with immune defense were significantly up-regulated after treatment, accompanied by increase in the number of CD8+ T lymphocytes, NK cells, and CD11b+ cells in SLR14-treated tumors. Strikingly, SLR14 dramatically inhibited nonimmunogenic B16 tumor growth, and the cured mice developed an immune memory. Furthermore, a systemic antitumor response was observed in both bilateral and tumor metastasis models. Collectively, our results demonstrate that SLR14 is a promising therapeutic RIG-I agonist for cancer treatment, either alone or in combination with existing immunotherapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligorribonucleotídeos
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Receptores de Superfície Celular
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Antineoplásicos
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2019
Tipo de documento:
Article