An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models

Burdelya, Lyudmila G.; Krivokrysenko, Vadim I.; Tallant, Thomas C.; Strom, Evguenia; Gleiberman, Anatoli S.; Gupta, Damodar; Kurnasov, Oleg V.; Fort, Farrel L.; Osterman, Andrei L.; DiDonato, Joseph A.; Feinstein, Elena; Gudkov, Andrei V.

doi:10.1126/science.1154986

articleScienceApr 10, 2008Closed access

An Agonist of Toll-Like Receptor 5 Has Radioprotective Activity in Mouse and Primate Models

LGLyudmila G. Burdelya VIVadim I. Krivokrysenko TCThomas C. Tallant ESEvguenia Strom ASAnatoli S. Gleiberman

Roswell Park Comprehensive Cancer Center · Sanford Burnham Prebys Medical Discovery Institute · +3 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

The toxicity of ionizing radiation is associated with massive apoptosis in radiosensitive organs. Here, we investigate whether a drug that activates a signaling mechanism used by tumor cells to suppress apoptosis can protect healthy cells from the harmful effects of radiation. We studied CBLB502, a polypeptide drug derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR5) and activates nuclear factor-kappaB signaling. A single injection of CBLB502 before lethal total-body irradiation protected mice from both gastrointestinal and hematopoietic acute radiation syndromes and resulted in improved survival. CBLB502 injected after irradiation also enhanced survival, but at lower radiation doses. It…

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697

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Topics & keywords

Topics

Keywords

TLR5
Cancer research
Ionizing radiation
Apoptosis
Receptor
Agonist
Pharmacology
Biology

UN Sustainable Development Goals

Good health and well-being

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