Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8 + T-cell axis
Abstract
Innate immune modulators can generate a potent antitumor T-cell response and are thus a desirable approach to immunotherapy. However, their use is limited by the risk of induction of acute inflammation. In this regard, bacterial flagellin is unique among other innate immune modulators because of a significantly safer cytokine profile induced upon activation by its target, Toll-like receptor 5 (TLR5). We show here that systemic administration of entolimod, a pharmacologically optimized flagellin derivative, induces a cascade of cell–cell signaling resulting in mobilization to the liver of various components of innate and adaptive immunity, followed by suppression of liver metastases and development of long-term antitumor immune memory. Thus, TLR5 agonists can be considered as an organ-specific immunotherapy for the treatment and prevention of metastases.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 01, 2016
- Source ID
- 10.1073/pnas.1521359113
Entities
People
- Andrei V. Gudkov
- Bojidar Kojouharov
- Craig M. Brackett
- Jean Veith
- Kellee F. Greene
- Lyudmila G. Burdelya
- Sandra O. Gollnick
- Scott I Abrams
Organizations
- Cleveland BioLabs
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of General Medical Sciences
- Roswell Park Comprehensive Cancer Center
- United States Department of Defense