Antifugetactic agents for the treatment of 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,

1 - 38 . (canceled) 
     
     
         39 . A pharmaceutical composition comprising:
 (a) one or more anti-fugetactic agents that specifically inhibit chemokine and/or chemokine receptor dimerization; and   (b) at least one suitable pharmaceutical excipient or carrier.   
     
     
         40 . The pharmaceutical composition of  claim 39 , wherein the one or more anti-fugetactic agents is a C-X-C chemokine receptor type 4 (CXCR4) antagonist, a CXCR3 antagonist, a CXCR4/stromal cell-derived factor 1 (SDF-1) antagonist or a selective protein kinase C (PKC) inhibitor. 
     
     
         41 . The pharmaceutical composition of  claim 40 , wherein the CXCR4 antagonist is AMD3100. 
     
     
         42 . The pharmaceutical composition of  claim 40 , wherein the CXCR3 antagonist is TAK-779. 
     
     
         43 . The pharmaceutical composition of  claim 40 , wherein the CXCR4/SDF-1 antagonist is Tannic acid. 
     
     
         44 . The pharmaceutical composition of  claim 40 , wherein the selective PKC inhibitor is thalidomide or GF109230X. 
     
     
         45 . The pharmaceutical composition of  claim 39 , wherein the one or more anti-fugetactic agents is an anti-cytokine- or a cytokine receptor antibody. 
     
     
         46 . A pharmaceutical composition comprising:
 (a) a fugetactic ligand dimer; and   (b) at least one suitable pharmaceutical excipient or carrier.   
     
     
         47 . The pharmaceutical composition of  claim 46 , wherein the ligand is SDF-1 or IL-8. 
     
     
         48 . A method for treating a subject in need thereof by administering the pharmaceutical composition of  claim 39 . 
     
     
         49 . A method for treating a subject in need thereof by administering the pharmaceutical composition of  claim 46 . 
     
     
         50 . The method of  claim 48 , wherein the subject has cancer. 
     
     
         51 . The method of  claim 50 , wherein the cancer is selected from biliary tract cancer; brain cancer; breast cancer; cervical cancer; choriocarcinoma; colon cancer; endometrial cancer; esophageal cancer, gastric cancer; hematological neoplasms; multiple myeloma; AIDS associated leukemias; adult T-cell leukemia lymphoma; intraepithelial neoplasms; liver cancer (hepatocarcinoma); lung cancer; lymphomas; neuroblastomas; oral cancer; ovarian cancer; pancreas cancer; prostate cancer; rectal cancer; sarcomas; skin cancer; testicular cancer; thyroid cancer; or renal cancer. 
     
     
         52 . The method of  claim 50 , further comprising inhibiting cell metastasis in the subject by administering to a tumor site in the subject the anti-fugetactic agent in an amount effective to decrease movement of tumor cells away from the tumor site, thereby inhibiting tumor cell metastasis in the subject and thereby treating cancer in the subject. 
     
     
         53 . The method of  claim 48 , wherein the treating the subject comprises enhancing an immune response. 
     
     
         54 . The method of  claim 43 , wherein the subject is infected with a pathogenic infection selected from a virus, bacteria, a parasite, or fungi. 
     
     
         55 . The method of  claim 48 , wherein the subject is human. 
     
     
         56 . The method of  claim 48 , further comprising administering a non-fugetactic agent to the subject. 
     
     
         57 . The method of  claim 56 , wherein the non-fugetactic is an anti-cancer agent, an immunosuppressant, or an inflammatory agent. 
     
     
         58 . The method of  claim 48 , wherein the administering is via oral administration, rectal administration, topical administration, nasal administration, interdermal administration, or parenteral administration.