Antifugetactic agents for the treatment of liver cancers

Abstract

This invention provides methods and compositions for modulating movement of eukaryotic cells with migratory capacity. More specifically, the invention provides anti-fugetactic agents and methods for the use thereof in enhancing an immune response.

What is claimed is: 
     
         1 . A method for mitigating immune cell-specific fugetactic activity of liver cancer in a mammal, which method comprises administering a pharmaceutical composition comprising an anti-fugetactic agent which targets CXCR4 receptors, wherein said composition is administered in an amount effective to mitigate the fugetactic activity of said cancer, wherein the administration is sustained so as to initiate and maintain mitigation of said fugetactic activity, and wherein said anti-fugetactic agent is 1,1′-[1,4-phenylenebis(methylene)]bis [1,4,8,11-tetraazacyclotetradecane]. 
     
     
         2 . The method of  claim 1 , wherein after said administration migration of immune cells to the cancer is increased. 
     
     
         3 . The method of  claim 2 , wherein the immune cells comprise T cells and wherein the T cells infiltrate the cancer. 
     
     
         4 . The method of  claim 1 , further comprising administering an anti-cancer agent to the mammal during mitigation of the fugetactic activity. 
     
     
         5 . The method of  claim 4 , wherein the anti-cancer agent is cisplatin. 
     
     
         6 . The method of  claim 4 , wherein the anti-cancer agent is paclitaxel. 
     
     
         7 . The method of  claim 1 , wherein the anti-fugetactic agent is in a sustained release formulation. 
     
     
         8 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         9 . The method of  claim 1 , wherein cancer size is reduced. 
     
     
         10 . The method of  claim 1 , wherein mitigation of the fugetactic activity comprises down-regulation of said fugetactic activity. 
     
     
         11 . The method of  claim 1 , wherein the effective amount is at least about 0.01 mg/kg/day. 
     
     
         12 . The method of  claim 1 , wherein the effective amount is about 0.01 mg/kg/day to about 100 mg/kg/day. 
     
     
         13 . The method of  claim 1 , wherein the effective amount is about 0.01 mg/kg/day to about 10 mg/kg/day. 
     
     
         14 . The method of  claim 1 , wherein said effective amount is about 0.08 mg/mL to about 0.25 mg/mL. 
     
     
         15 . The method of  claim 1 , wherein said cancer is a hepatocarcinoma. 
     
     
         16 . A method for treating liver cancer in a mammal, said cancer having a fugetactic activity, which method comprises administering a pharmaceutical composition comprising an anti-fugetactic agent which targets CXCR4 receptors in an amount effective to mitigate the fugetactic activity of said cancer, wherein the administration is sustained so as to initiate and maintain mitigation of said fugetactic activity, wherein said anti-fugetactic agent is 1,1′-[1,4-phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane], and further comprising administering to said mammal an anti-cancer agent so as to treat the cancer. 
     
     
         17 . The method of  claim 16 , wherein the anti-cancer agent is cisplatin. 
     
     
         18 . The method of  claim 16 , wherein the anti-cancer agent is paclitaxel. 
     
     
         19 . The method of  claim 16 , wherein said liver cancer is a hepatocarcinoma. 
     
     
         20 . The method of  claim 16  wherein said anti-cancer agent is administered during mitigation of the fugetactic activity. 
     
     
         21 . A method for mitigating immune cell-specific fugetactic activity of liver cancer in a mammal, which method comprises administering 1,1′-[1,4-phenylenebis(methylene)]bis [1,4,8,11-tetraazacyclotetradecane].