Methods and products related to metabolic interactions in disease

Abstract

The invention involves methods of regulating cell growth and division to control disease processes by manipulating mitochondrial metabolism and the expression of cell surface immune proteins. The invention also involves related compositions and screening assays.

1 . A method for decreasing mitochondrial membrane potential in a mammalian cell, comprising
 administering an MHC class II HLA-DR ligand to the mammalian cell to selectively engage MHC class II HLA-DR on the surface of the cell in an amount effective to decrease mitochondrial membrane potential in the mammalian cell, wherein the mammalian cell is not an antigen presenting cell.   
     
     
         2 - 4 . (canceled) 
     
     
         5 . A method for inducing-apoptosis in a tumor cell, comprising:
 contacting a tumor cell with an amount of a metabolic modifying agent, which when exposed to a cell causes coupling of electron transport and oxidative phosphorylation, effective to increase the mitochondrial membrane potential in the tumor cell, and   contacting the tumor cell with an amount of an apoptotic chemotherapeutic agent effective for inducing apoptosis in the tumor cell.   
     
     
         6 . The method of  claim 5 , wherein the metabolic modifying agent is a glucose. 
     
     
         7 . The method of  claim 5 , wherein the metabolic modifying agent is an MHC class II HLA-DP/DQ ligand. 
     
     
         8 . The method of  claim 5 , wherein the metabolic modifying agent is selected from the group consisting of phorbol myristate acetate in combination with ionomycin, GDP, CD40 binding peptide, sodium acetate, UCP antisense, dominant negative UCP, and staurosporine. 
     
     
         9 . The method of  claim 5 , wherein the metabolic modifying agent is GDP. 
     
     
         10 . The method of  claim 5 , wherein the apoptotic chemotherapeutic agent is a taxol. 
     
     
         11 . The method of  claim 5 , wherein the metabolic modifying agent and the apoptotic chemotherapeutic agent are administered simultaneously. 
     
     
         12 . The method of  claim 5 , wherein the metabolic modifying agent and the apoptotic chemotherapeutic agent are administered locally. 
     
     
         13 . The method of  claim 11 , wherein the tumor cell is resistant to the apoptotic chemotherapeutic agent. 
     
     
         14 . The method of  claim 5 , wherein the tumor cell is sensitive to the apoptotic chemotherapeutic agent, and wherein the amount of metabolic modifying agent is effective to increase mitochondrial membrane potential and the amount of apoptotic chemotherapeutic agent is effective to inhibit the proliferation of the tumor cell when the mitochondrial membrane potential is increased. 
     
     
         15 - 27 . (canceled) 
     
     
         28 . A method for treating human breast cancer which contains metabolizing cells, said method comprising the steps of administering to a subject:
 (a) a taxol for killing at least some of the cells; and   (b) a glucose for killing at least some of the cells.   
     
     
         29 . The method of  claim 28 , wherein the glucose is a glucose analog. 
     
     
         30 . The method of  claim 29 , wherein the glucose analog is 2-Deoxy-D-glucose. 
     
     
         31 . A method for treating human breast cancer which contains metabolizing cells, said method comprising the steps of administering to a subject:
 (a) a chemotherapeutic agent for killing at least some of the cells; and   (b) a metabolic modifying agent for killing at least some of the cells.   
     
     
         32 . A method for treating human breast cancer which contains both aerobically and anaerobically metabolizing cells, said method comprising the steps of administering to a patient in need thereof:
 (a) at least one of docataxel and paclitaxel; and   (b) 2-Deoxy-D-glucose.