On January 28, 2010, Cleveland BioLabs, Inc. announced that the European Patent Office granted them a patent, "Methods of Protecting Against Radiation Using Flagellin". This patent had already been granted in the United States and 11 other countries. This patent covers the method of protecting a mammal from radiation using flagellin or its derivatives, like CBLB502 (Levine, 2010).
CBLB binds to Toll-like receptor 5 (TLR5) and turns on the nuclear factor-κB signalling pathway. This results in the induction of factors that protect cells like apoptosis inhibitors and promotes tissue regeneration through cytokines. The drug also inhibits the p53 tumour suppression pathway which is a mechanism by which cancer cells resist radiation.
Radiation is toxic because of the massive apoptosis it causes in radiosensitive organs. CBLB502 operates on the principle that radioprotection is achieved through suppression of apoptosis. CBLB502 protects healthy cells from the harmful effects of radiation, all while allowing the tumours to be better affected by the radiation.
High-dose ionizing radiation can cause acute radiation syndromes involving the hematopoietic system and the gastrointestinal tract. CBLB502 was effective as a radioprotectant in 19 monkeys who were subjected to 6.5 Gy total body irradiation, which is a lethal dose for 70% of monkeys (LD70). The monkeys received an injection of 0.04mg of CBLB502 45 minutes before the irradiation. This reduced the onset of radiation-induced mortality by 10 days and increased the 40-day survival rate from 25% to 64%. The 7 monkeys who survived 40 days post-irradiation demonstrated minor damage to major hematopoietic and lymphoid organs, the bone marrow, spleen and thymus (Burdelya, et al., 2008).
Burdelya, et al. (2008) assessed CBLB502 as an adjuvant for anticancer radiotherapy. CBLB502 was injected into mice 1 hour before each of three daily treatments of 4 Gy total body irradiation. The treatment completely prevented radiation-induced mortality or significantly protected against it. The implication of this is that the drug could be used in patients receiving radiotherapy to protect against the adverse effects. The adverse effects of radiation must be managed by limiting the dose applied. If the adverse effects were eliminated, higher doses could be used.
Another interesting application of the drug is treatment post lethal irradiation. Mice who were exposed to lethal radiation (13 Gy) were rescued by CBLB502 treatment 6 months later. The mice showed signs of radiation-induced tissue damage but had no signs of cancer (Burdelya, et al., 2008).
CBLB502 is still in the early stages of development but it could allow for safer and more effective radiation therapy and protection in overexposures to radiation.
Levine, R. (2010, January 28). Cleveland BioLabs granted European patent for radiation protection drug CBLB502. CNN. Retrieved from http://money.cnn.com/news/newsfeeds/articles/marketwire/0581289.htm
CBLB binds to Toll-like receptor 5 (TLR5) and turns on the nuclear factor-κB signalling pathway. This results in the induction of factors that protect cells like apoptosis inhibitors and promotes tissue regeneration through cytokines. The drug also inhibits the p53 tumour suppression pathway which is a mechanism by which cancer cells resist radiation.
Radiation is toxic because of the massive apoptosis it causes in radiosensitive organs. CBLB502 operates on the principle that radioprotection is achieved through suppression of apoptosis. CBLB502 protects healthy cells from the harmful effects of radiation, all while allowing the tumours to be better affected by the radiation.
High-dose ionizing radiation can cause acute radiation syndromes involving the hematopoietic system and the gastrointestinal tract. CBLB502 was effective as a radioprotectant in 19 monkeys who were subjected to 6.5 Gy total body irradiation, which is a lethal dose for 70% of monkeys (LD70). The monkeys received an injection of 0.04mg of CBLB502 45 minutes before the irradiation. This reduced the onset of radiation-induced mortality by 10 days and increased the 40-day survival rate from 25% to 64%. The 7 monkeys who survived 40 days post-irradiation demonstrated minor damage to major hematopoietic and lymphoid organs, the bone marrow, spleen and thymus (Burdelya, et al., 2008).
Burdelya, et al. (2008) assessed CBLB502 as an adjuvant for anticancer radiotherapy. CBLB502 was injected into mice 1 hour before each of three daily treatments of 4 Gy total body irradiation. The treatment completely prevented radiation-induced mortality or significantly protected against it. The implication of this is that the drug could be used in patients receiving radiotherapy to protect against the adverse effects. The adverse effects of radiation must be managed by limiting the dose applied. If the adverse effects were eliminated, higher doses could be used.
Another interesting application of the drug is treatment post lethal irradiation. Mice who were exposed to lethal radiation (13 Gy) were rescued by CBLB502 treatment 6 months later. The mice showed signs of radiation-induced tissue damage but had no signs of cancer (Burdelya, et al., 2008).
CBLB502 is still in the early stages of development but it could allow for safer and more effective radiation therapy and protection in overexposures to radiation.
Levine, R. (2010, January 28). Cleveland BioLabs granted European patent for radiation protection drug CBLB502. CNN. Retrieved from http://money.cnn.com/news/newsfeeds/articles/marketwire/0581289.htm
Burdelya, L. G., Krivokrysenko, V. I., Tallant, T. C., Strom, E., Gleiberman, A. S., Gupta, D., … Gudkov, A. V. (2008). An agonist of toll-like receptor 5 has radioprotective activity in primate models. Science, 320(5873), 226-230. Retrieved from http://www.sciencemag.org.ezproxy.library.dal.ca/cgi/content/full/320/5873/226
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