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

A research group from the Roswell Park Cancer Institute (USA) investigated the suppressive effect of a chemical compound on apoptosis from tumour cells in relation to healthy cells exposed to harmful radiation.

Ionising radiation leads to massive apoptosis in radiosensitive organs. Now a drug that can activate apoptosis suppressing mechanisms used by tumour cells was tested for its protecting effect on healthy cells exposed to harmful doses of radiation.

The scientists used the polypeptide drug CBLB502 for their study. CBLB502 is derived from Salmonella flagellin that binds to Toll-like receptor 5 (TLR-5) and activates nuclear factor–κB signalling. A single injection of the drug was sufficient to protect mice from gastrointestinal as well as hematopoietic acute radiation syndromes and resulted in improved survival, if the drug was injected before lethal total-body irradiation.

If CBLB502 was injected after irradiation it also enhanced survival, but only at lower radiation doses. The drug, however, did not decrease tumor radiosensitivity in mouse models.

CBLB502 also seems to express radioprotective activity in lethally irradiated rhesus monkeys. TLR-5 agonists could therefore be a benefit for the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies.

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TLR-5

Salmonella

Salmonella Flagellin

NF-κ-B

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