An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models

被引：583

作者：

Burdelya, Lyudmila G. ^{[2
]}

Krivokrysenko, Vadim I. ^{[1
]}

Tallant, Thomas C. ^{[3
]}

Strom, Evguenia ^{[1
]}

Gleiberman, Anatoly S. ^{[1
]}

Gupta, Damodar ^{[2
]}

Kurnasov, Oleg V. ^{[4
]}

Fort, Farrel L. ^{[1
]}

Osterman, Andrei L. ^{[4
]}

DiDonato, Joseph A. ^{[3
]}

Feinstein, Elena ^{[1
]}

Gudkov, Andrei V. ^{[1
,2
]}

机构：

[1] Cleveland Biolabs Inc CBLI, Buffalo, NY 14203 USA

[2] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA

[3] Cleveland Clin, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA

[4] Burnham Inst, La Jolla, CA 92037 USA

来源：

SCIENCE | 2008年 / 320卷 / 5873期

关键词：

D O I：

10.1126/science.1154986

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-kappa B 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.

引用

页码：226 / 230

页数：5

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