Flagellin related polypeptides and uses thereof

Abstract

The use of flagellin and flagellin related polypeptides for the protection of mammals from the effects of apoptosis is described.

1 .- 13 . (canceled) 
     
     
         14 . A method of treating apoptosis-mediated tissue damage in a patient comprising administering to a mammal in need thereof a composition comprising a flagellin polypeptide, wherein the polypeptide comprises an amino terminal domain comprising amino acids 1-163 of SEQ ID NO: 1 and a carboxyl terminal domain comprising amino acids 402-450 of SEQ ID NO: 1, wherein the amino terminal and the carboxyl terminal domains are linked by a polypeptide linker that does not comprise amino acids 177-401 of SEQ ID NO: 1, and wherein the apoptosis is attributable to radiation. 
     
     
         15 . The method of  claim 14 , wherein the carboxyl terminal domain comprises amino acids 402-505 of SEQ ID NO: 1. 
     
     
         16 . The method of  claim 14 , wherein the amino terminal domain comprises amino acids 1-176 of SEQ ID NO: 1. 
     
     
         17 . The method of  claim 14 , wherein the polypeptide linker comprises the  E. coli  hinge region (ECH) of  E. coli  MukB protein. 
     
     
         18 . The method of  claim 14 , wherein the polypeptide linker comprises a sequence selected from the group consisting of SEQ ID NOs: 3 and 4. 
     
     
         19 . The method of  claim 14 , wherein the composition is administered in combination with a radioprotectant. 
     
     
         20 . The method of  claim 19 , wherein the radioprotectant is an antioxidant. 
     
     
         21 . The method of  claim 20 , wherein the antioxidant is selected from the group consisting of amifostine and vitamin E. 
     
     
         21 . The method of  claim 19 , wherein the radioprotectant is a cytokine. 
     
     
         22 . The method of  claim 21 , wherein the cytokine is a stem cell factor. 
     
     
         23 . The method of  claim 19 , wherein the radioprotectant is a growth factor. 
     
     
         24 . The method of  claim 23 , wherein the growth factor is keratinocyte growth factor. 
     
     
         25 . The method of  claim 19 , wherein the radioprotectant is a steroid. 
     
     
         26 . The method of  claim 25 , wherein the steroid is 5-androstenediol. 
     
     
         27 . The method of  claim 19 , wherein the radioprotectant is ammonium trichloro(dioxoethylene-O,O′)tellurate. 
     
     
         28 . The method of  claim 14 , wherein the radiation is cancer radiotherapy. 
     
     
         29 . The method of  claim 14 , wherein the composition is administered prior to, together with, or after radiation.