COMPOSITIONS AND METHODS FOR TREATING DISEASE USING SALMONELLA T3SS EFFECTOR PROTEIN (SipA)

Abstract

The invention provides compositions and methods for reducing one or more symptoms of disease by administering compositions comprising SipA. The invention's compositions and methods are particularly advantageous in reducing symptoms of diseases that are associated with overexpression of P-gp and/or p53. The invention's compositions and methods are useful in reducing cancer symptom and/or cancer multidrug resistance (MDR). The invention provides a method for reducing one or more symptoms of cancer in a mammalian subject in need thereof, comprising administering to said subject a composition comprising purified SipA. In one embodiment, said SipA is operably conjugated to a nanoparticle. In another embodiment, said cancer comprises cancer cells resistant to at least one cytotoxin.

1 . A method for reducing one or more symptoms of cancer in a mammalian subject in need thereof, comprising administering to said subject
 (a) a composition comprising purified SipA operably conjugated to a targeting agent that specifically binds to cells of said cancer, and   (b) One or more cytotoxins,   said administering reduces said one or more symptoms of said cancer.   
     
     
         2 . The method of  claim 1 , wherein said SipA is operably conjugated to a nanoparticle. 
     
     
         3 . The method of  claim 1 , wherein said cancer comprises cancer cells resistant to at least one cytotoxin. 
     
     
         4 . The method of  claim 1 , wherein said cancer comprises cancer cells that overexpress one or more of P-gp and p53 compared to a control cell. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , wherein said SipA is administered in an amount that is effective in one or more of
 a) reducing the level of expression of P-gp in cells of said cancer,   b) reducing the level of un-cleaved P-gp in cells of said cancer, and   c) increasing the level of expression of PERP in cells of said cancer.   
     
     
         7 . The method of  claim 1 , wherein said method further comprises determining the level of expression of P-gp in cells of said cancer. 
     
     
         8 . The method of  claim 1 , wherein said SipA is operably conjugated to a cytotoxin. 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 9 , wherein said targeting agent comprises an antibody, or an antigen-binding portion thereof. 
     
     
         11 . The method of  claim 9 , wherein said targeting agent comprises cyclic-arginine-glycine-aspartic acid (cRGD) peptide. 
     
     
         12 . The method of  claim 9 , wherein said targeting agent comprises folic acid. 
     
     
         13 . A method for reducing one or more symptoms of cancer in a mammalian subject in need thereof, wherein said disease is associated with cells that overexpress one or more of P-gp and p53, said method comprising administering to said subject
 a) a composition comprising purified SipA conjugated to a targeting agent that specifically binds to cells of said cancer, and   (b) one or more cytotoxin,   
       wherein said SipA is in an amount that is effective in one or more of
 a) reducing the level of expression of P-gp in said cells, 
 b) reducing the level of un-cleaved P-gp in said cells, and 
 c) increasing the level of expression of PERP in said cells, and 
 
       wherein said administering reduces said one or more symptoms of said cancer. 
     
     
         14 - 22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein said cancer is selected from the group consisting of colon cancer, breast cancer, intestinal cancer, and bladder cancer. 
     
     
         24 . The method of  claim 1 , said cytotoxin comprises doxorubicin. 
     
     
         25 . The method of  claim 8 , said cytotoxin comprises doxorubicin. 
     
     
         26 . The method of  claim 1 , said cancer symptom comprises tumor volume. 
     
     
         27 . The method of  claim 8 , said cancer symptom comprises tumor volume. 
     
     
         28 . The method of  claim 13 , wherein said cancer is selected from the group consisting of colon cancer, breast cancer, intestinal cancer, and bladder cancer. 
     
     
         29 . The method of  claim 13 , said cytotoxin comprises doxorubicin. 
     
     
         30 . The method of  claim 13 , said cancer symptom comprises tumor volume.