Intratumoral delivery of RIG-I agonist SLR14 induces robust antitumor responses

J Exp Med. 2019 Dec 2;216(12):2854-2868. doi: 10.1084/jem.20190801. Epub 2019 Oct 10.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents, Immunological / pharmacology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Profiling
  • Immunologic Memory
  • Injections, Intralesional
  • Male
  • Melanoma, Experimental
  • Mice
  • Oligoribonucleotides / administration & dosage
  • Oligoribonucleotides / pharmacology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Receptors, Cell Surface / antagonists & inhibitors*
  • Tumor Burden / drug effects


  • Antineoplastic Agents
  • Antineoplastic Agents, Immunological
  • Oligoribonucleotides
  • Programmed Cell Death 1 Receptor
  • Receptors, Cell Surface
  • Robo3 protein, mouse