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

Overview

Journal Science

Specialty Science

Date 2008 Apr 12

PMID 18403709

Citations 337

Authors

Lyudmila G Burdelya

Vadim I Krivokrysenko

Thomas C Tallant

Evguenia Strom

Anatoly S Gleiberman

Damodar Gupta

Oleg V Kurnasov

Farrel L Fort

Andrei L Osterman

Joseph A DiDonato

Elena Feinstein

Andrei V Gudkov

Affiliations

Soon will be listed here.

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 is noteworthy that the drug did not decrease tumor radiosensitivity in mouse models. CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.

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