Anti-fugetactic agent and anti-cancer agent combination therapy and compositions for the treatment of cancer

Abstract

The invention described herein relates to methods and compositions for treating cancer in a patient or a tumor cell by administering an effective amount of an anti-fugetactic agent and an additional anti-cancer agent.

What is claimed is: 
     
         1 . A method for killing a cancer cell expressing an amount of a chemokine sufficient to produce a fugetactic effect, which method comprises:
 a) periodically contacting said cell with an effective amount of an anti-fugetactic agent for a sufficient period of time so as to inhibit said fugetactic effect;   b) contacting said cell with at least one anti-cancer agent, wherein steps a) and b) are done in sequential order; and   c) optionally repeating steps a) and b) as necessary to kill said cell.   
     
     
         2 . The method of  claim 1 , wherein said chemokine is CXCL12 or interleukin 8. 
     
     
         3 . The method of  claim 1 , wherein said cancer cell is a solid tumor cell. 
     
     
         4 . The method of  claim 1 , wherein said cancer cell is a leukemia cell. 
     
     
         5 . The method of  claim 1 , wherein said anti-fugetactic agent is selected from the group consisting of AMD3100, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, Tannic acid, NSC 651016, thalidomide, and GF 109230X. 
     
     
         6 . The method of  claim 1 , wherein said anti-cancer agent is selected from the group consisting of a chemotherapeutic agent, a radiotherapeutic agent, and an anti-cancer vaccine. 
     
     
         7 . The method of any one of  claims 1 - 6 , wherein said therapy is initiated within 3 days of completion of contacting the cell with the anti-fugetactic agent. 
     
     
         8 . The method of any one of  claims 1 - 6 , wherein said therapy is initiated the day after completion of contacting the cell with the anti-fugetactic agent. 
     
     
         9 . A method for treating a solid tumor in a mammal which tumor expresses a chemokine at a concentration sufficient to produce a fugetactic effect, which method comprises administering to said mammal an effective amount of an anti-fugetactic agent for a sufficient period of time so as to inhibit said fugetactic effect, followed by administering to said mammal at least one anti-cancer agent. 
     
     
         10 . The method of  claim 9 , wherein said chemokine is CXCL12 or interleukin 8. 
     
     
         11 . The method of  claim 9 , wherein said tumor is a leukemia. 
     
     
         12 . The method of  claim 9 , wherein said anti-fugetactic agent is selected from the group consisting of AMD3100, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, Tannic acid, NSC 651016, thalidomide and GF 109230X. 
     
     
         13 . The method of  claim 9 , wherein said anti-cancer agent is selected from the group consisting of a chemotherapeutic agent, a radiotherapeutic agent, and an anti-cancer vaccine. 
     
     
         14 . The method of any one of  claims 9 - 13 , wherein said therapy is initiated within 3 days of administering the anti-fugetactic agent. 
     
     
         15 . The method of any one of  claims 9 - 13 , wherein said therapy is initiated the day after completion of administering the anti-fugetactic agent. 
     
     
         16 . The method of any one of  claims 9 - 15 , wherein metastasis of a cell from the tumor is inhibited. 
     
     
         17 . A method for killing a cancer stem cell in a mammal, the method comprising administering to said mammal an effective amount of an anti-fugetactic agent for a sufficient period of time so as to induce said cancer stem cell to enter the circulatory system of the mammal, followed by administering to said mammal an effective amount of at least one anti-cancer agent to kill the cancer stem cell. 
     
     
         18 . The method of  claim 17 , wherein said anti-fugetactic agent is selected from the group consisting of AMD3100, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, Tannic acid, NSC 651016, thalidomide and GF 109230X. 
     
     
         19 . The method of  claim 17  or  claim 18 , wherein said anti-cancer agent is selected from the group consisting of a chemotherapeutic agent, a radiotherapeutic agent, and an anti-cancer vaccine. 
     
     
         20 . A method to locally treat a solid tumor expressing a chemokine at a concentration sufficient to produce a fugetactic effect in a patient, which method comprises delivering an anti-fugetactic agent to the solid tumor followed by an anti-cancer agent which method comprises:
 a) identifying an artery or microartery feeding said tumor;   b) intra-arterially placing a catheter or microcatheter in said artery or microartery proximal to the flow of blood into said tumor wherein said catheter or microcatheter comprising a lumen for delivering a fluid there through and means for delivering said fluid;   c) periodically administering an effective amount of the anti-fugetactic agent through said catheter or said microcatheter to the artery or microartery feeding said tumor so as to inhibit said fugetactic effect; and   d) subsequently administering an effective amount of the anti-cancer agent to the patient.   
     
     
         21 . The method of  claim 20 , wherein step d) further comprises administering the anti-cancer agent using a catheter, a microcatheter, an external radiation source, or via injection or implantation proximal to or within the tumor. 
     
     
         22 . The method of  claim 20  or  claim 21 , further comprising:
 e) repeating steps a)-d) until the patient's condition improves. 
 
     
     
         23 . The method of  claim 20 , wherein the tumor is a brain tumor. 
     
     
         24 . The method of  claim 20  or  claim 21 , wherein said anti-cancer agent is selected from the group consisting of a chemotherapeutic agent, a radiotherapeutic agent, and an anti-cancer vaccine. 
     
     
         25 . The method of  claim 24 , wherein the anti-cancer agent is a radiotherapeutic agent, the amount of said radiotherapeutic agent being sufficient to ablate a blood vessel feeding said tumor. 
     
     
         26 . The method of any one of  claims 1 - 25 , comprising the steps of:
 a) administering the anti-fugetactic agent over a period of about 2 days to about 10 days; and   b) administering the anti-cancer agent over a period of about 2 days to about 10 days following the period of administration of the anti-fugetactic agent.   
     
     
         27 . The method of  claim 26 , further comprising repeating steps a) and b) until the condition of said patient improves. 
     
     
         28 . The method of any one of  claims 1 - 27 , wherein the anti-fugetactic agent is administered subdermally, intra-arterially, or intravenously. 
     
     
         29 . The method of any one of  claims 1 - 28 , wherein the anti-cancer agent is administered subdermally, intra-arterially, or intravenously. 
     
     
         30 . A solid tumor cell expressing CXCL12 which has been contacted with an anti-fugetactic agent and a chemotherapeutic agent. 
     
     
         31 . The cell of  claim 30 , wherein the anti-fugetactic agent is selected from the group consisting of AMD3100, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, Tannic acid, NSC 651016, thalidomide, and GF 109230X. 
     
     
         32 . A kit of parts comprising a first container comprising an anti-fugetactic agent and a second container comprising an anti-cancer agent. 
     
     
         33 . The kit of parts of  claim 32 , wherein the anti-fugetactic agent is an inhibitor of CXCL12, an inhibitor of CXCR3, or an inhibitor of CXCR4. 
     
     
         34 . The kit of parts of  claim 32 , wherein the anti-fugetactic agent is selected from the group consisting of AMD3100, KRH-1636, T-20, T-22, T-140, TE-14011, T-14012, TN14003, TAK-779, AK602, SCH-351125, Tannic acid, NSC 651016, thalidomide, and GF 109230X. 
     
     
         35 . The kit of parts of  claim 32 , wherein the anti-cancer agent is selected from the group consisting of an immunotherapeutic agent, a chemotherapeutic agent, a radiotherapeutic agent, a cancer vaccine, or any combination thereof.