Methods for the modulation of the growth of collateral arteries and/or other arteries from preexisting arteriolar connections

Abstract

Described is the modulation of the growth of collateral arteries and/or other arteries from preexisting arteriolar connections. Methods are provided for enhancing the growth of collateral arteries and/or other arteries from preexisting arteriolar connections comprising contacting tissue or cells with a monocyte chemotactic protein (MCP) or a nucleic acid molecule encoding said MCP. Furthermore, the use of a MCP or a nucleic acid molecule encoding said MCP for the preparation of pharmaceutical compositions for enhancing collateral growth of collateral arteries and/or other arteries from preexisting arteriolar connections is described. Also provided are methods for the treatment of tumors comprising contacting tissue or cells with an agent which suppresses the growth of collateral arteries and/or other arteries from preexisting arteriolar connections through the attraction of monocytes. Described is further the use of an agent which suppresses the growth of collateral arteries and/or other arteries from preexisting arteriolar connections through attraction of monocytes for the preparation of pharmaceutical compositions for the treatment of tumors.

1 . A method for enhancing the growth of collateral arteries and/or other arteries from preexisting arteriolar connections comprising contacting tissue or cells with a monocyte chemotactic protein (MCP) or a nucleic acid molecule encoding said MCP.  
     
     
         2 . Use of a monocyte chemotactic protein (MCP) or a nucleic acid molecule encoding said MCP for the preparation of a pharmaceutical composition for enhancing collateral growth of collateral arteries and/or other arteries from preexisting arteriolar connections.  
     
     
         3 . The method of  claim 1  or the use of  claim 2 , wherein said MCP is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP4, MIP-1α, RANTES, J-309 or any other CC-chemokine or classical chemoattractants like N-farnesyl peptides, C5a, leukotriene B4 or Platelet-activating factor (PAF).  
     
     
         4 . The method of  claim 1  or  3  or the use of  claim 2  or  3  for the treatment of subjects suffering from occlusive diseases.  
     
     
         5 . The method or the use of  claim 4 , wherein the occlusive disease is an arterial occlusive disease selected from the group consisting of coronary artery diseases, cerebral occlusive diseases, peripheral occlusive diseases, visceral occlusive diseases, renal artery diseases and mesenterial arterial insufficiency.  
     
     
         6 . The method of  claim 1  or  3  or the use of  claim 2  or  3  for the treatment of subjects during or after exposure to an agent or radiation or surgical treatment which damage or destroy arteries.  
     
     
         7 . The method of any one of claims  1  or  3  to  6  or the use of any one of  claims 2  to  6 , wherein the MCP is a recombinant MCP.  
     
     
         8 . The use of any one of  claims 2  to  7 , wherein the pharmaceutical composition is designed for administration in conjugation with growth factors like fibroblast growth factor or vascular endothelial growth factor.  
     
     
         9 . The method of any one of claims  1  or  3  to  7 , comprising 
 (a) obtaining cells from a subject;  
 (b) introducing a nucleic acid molecule encoding the MCP into said cells, thereby conferring expression and secretion of the MCP in a form suitable for the attraction of monocytes; and  
 (c) reintroducing the cells obtained in step (b) into the subject.  
 
     
     
         10 . The use of any one of  claims 2  to  8 , wherein the nucleic acid molecule in the pharmaceutical composition is designed for the expression and secretion of the MCP by cells in vivo in a form suitable for the attraction of monocytes.  
     
     
         11 . A method for the treatment of tumors comprising contacting tissue or cells with an agent which suppresses the growth of collateral arteries and/or other arteries from preexisting arteriolar connections through the attraction of monocytes.  
     
     
         12 . Use of an agent which suppresses the growth of collateral arteries and/or other arteries from preexisting arteriolar connections through the attraction of monocytes for the preparation of a pharmaceutical composition for the treatment of tumors.  
     
     
         13 . The method of  claim 11  or the use of  claim 12  wherein the agent inhibits the biological activity of a MCP and/or inhibits an intracellular signal triggered in the monocytes through the receptor for a MCP.  
     
     
         14 . The method or the use of  claim 13 , wherein the agent blocks an interaction of the MCP and its receptor.  
     
     
         15 . The method or the use of  claim 14 , wherein the receptor is selected from the group consisting of CCR1, CCR2, CCR4 and CCR5.  
     
     
         16 . The method or the use of  claim 14  or  15 , wherein the agent which blocks an interaction of the MCP and its receptor is selected from the group consisting of 
 (i) an anti-MCP antibody and an anti-MCP-receptor antibody; and/or  
 (ii) a non-stimulatory form of an MCP protein and a soluble form of an MCP-receptor.  
 
     
     
         17 . The method of  claim 11  or the use of  claim 12 , wherein the agent is an antisense RNA of the MCP or of its receptor.  
     
     
         18 . The method or the use of  claim 17 , wherein the antisense RNA is designed to be expressed in vascular cells or cells surrounding preexisting arteriolar connections to a tumor.  
     
     
         19 . The method of any one of claims  11  or  13  to  18  or the use of any one of  claims 12  to  18 , wherein the tumor is a vascular tumor.  
     
     
         20 . The method or the use  claim 19 , wherein the tumor is selected form the group consisting of Colon Carcinoma, Sarcoma, Carcinoma in the breast, Carcinoma in the head/neck, Mesothelioma, Glioblastoma, Lymphoma and Meningeoma.  
     
     
         21 . The use of any one of  claims 2  to  8  or  12  to  20 , wherein the pharmaceutical composition is designed for administration by catheter intraarterial, intravenous, intraperitoneal or subcutenous routes.