In summary, CBLB502 reduces radiation toxicity without diminishing the therapeutic antitumor effect of radiation and without promoting radiation-induced carcinogenicity. These properties of a TLR5 agonist acting as an NF-B–inducing agent provide further support for our concept of pharmacological imitation of tumor-specific antiapoptotic mechanisms as an approach to radioprotection. This approach was first validated by our demonstration that a chemical inhibitor of the proapoptotic p53 pathway safeguarded mice from lethal acute radiation syndrome. However, we subsequently found that wild-type p53 plays an unexpected role as a survival factor in GI cells exposed to high doses of -irradiation, limiting the usefulness of p53 inhibitors to protection against HP, but not GI, acute radiation syndrome. This problem has been resolved by our identification of CBLB502 as a TLR5 agonist that can protect against both major acute radiation syndromes. Our results suggest that TLR5 agonists may be valuable as both adjuvants for cancer radiotherapy and protectants or mitigators for radiation emergencies.This is pretty spectacular. Animal studies showed a marked increase in survival rates at very high radiation doses- 13 Gy for the mice and 6.5 Gy for the Rhesus monkeys. The most obvious use of the drug is to to protect cancer patients from the effects of radiotherapy- amazingly, it doesn't appear to impact the radiosensitivity of tumors- but it also has potential emergency management applications.
Effective radioprotective drugs were one of the holy grails of civil defense researchers back in the 1950s. The hope was that these drugs could make fallout protection more practical by reducing shelter requirements. Optimists dreamed of drugs that would make fallout shelters unnecessary. High hopes were soon dashed, however. The few radioprotective agents discovered were unable to provide protection against acute radiation poisoning- the circumstance that interested civil defense. Soviet civil defense retained more interest in the idea, and issued an "individual first aid kit" containing drugs for use by individuals in a major war. It contained antibiotics, anti-vomiting medication, nerve gas antidote pills (!), several "anti-radiation drugs" (I have yet to identify exactly what), and a syringe full of morphine.
If CBLB502 can be made into a practical emergency management tool, it could make mass radiation protection much more practical. In particular, it could reduce the immediate needs for sheltering and evacuation following a radiological dispersal event enormously. It's not an absolute panacea- due to the way the drug works it is probably unsafe for children and pregnant women. But it could turn the unsolvable nightmare of protecting the people of a densely populated area from radiation poisoning into a manageable scenario. That's pretty impressive.