Materials and Methods Useful For Treating Glioblastoma

Abstract

The present invention provides compositions and methods useful for treating cancers such as glioblastoma. SapC-DOPS was found to be synergistically effective at inducing cell death when administered in conjunction with rampamycin. SapC-DOPS/rapamycin combination therapy allows physicians to give lower doses of each drug and achieve better therapeutic efficacy. The compositions also allow for less toxicity and fewer off-target effects. Related methods and materials are also provided herein.

What is claimed is: 
     
         1 . A composition of matter comprising:
 an anionic phospholipid;   a polypeptide derived from Saposin C, wherein the anionic phospholipid incorporates the polypeptide in a nanovesicle;   a mTOR inhibitor; and   a pharmaceutically acceptable carrier.   
     
     
         2 . The composition of  claim 1 , wherein the mTOR inhibitor is selected from the group consisting of: (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21 S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[(1R)-2-[(1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone (sirolimus), 40-O-(2-Hydroxyethyl)rapamycin (everolimus), 40-O-Benzyl-rapamycin, 40-O-(4′-Hydroxymethyl)benzyl-rapamycin, 40-O-[4′-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 40-O-Allyl-rapamycin, 40-O-[3′-(2,2-Dimethyl-1,3-dioxolan-4(S)-yl)-prop-2′-en-1′-yl]-rapamycin, (2′:E,4′S)-40-O-(4′,5′-Dihydroxypent-2′-en-1′-yl)-rapamycin, 40-O-(2-Hydroxy)ethoxycarbonylmethyl-rapamycin, 40-O-(3-Hydroxy)propyl-rapamycin, 40-O-(6-Hydroxy)hexyl-rapamycin, 40-O-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin, 40-O-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 40-O-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 40-O-(2-Acetoxy)ethyl-rapamycin, 40-O-(2-Nicotinoyloxy)ethyl-rapamycin, 40-O-[2-(N-Morpholino)acetoxy]ethyl-rapamycin, 40-O-(2-N-lmidazolylacetoxy)ethyl-rapamycin, 40-O-[2-(N-Methyl-N′-piperazinyl)acetoxy]ethyl-rapamycin, 39-O-Desmethyl-39,40-O,O-ethylene-rapamycin, (26R)-26-Dihydro-40-O-(2-hydroxy)ethyl-rapamycin, 28-O-Methyl-rapamycin, 40-O-(2-Aminoethyl)-rapamycin, 40-O-(2-Acetaminoethyl)-rapamycin, 40-O-(2-Nicotinamidoethyl)-rapamycin, 40-O-(2-(N-Methyl-imidazo-2′-ylcarbethoxamido)ethyl)-rapamycin, 40-O-(2-Ethoxycarbonylaminoethyl)-rapamycin, 40-O-(2-Tolylsulfonamidoethyl)-rapamycin), 40-O-[2-(4′,5′-Dicarboethoxy-r,2′,3′-triazol-1′-yl)-ethyl]-rapamycin, 42-deoxy-42-(1H-tetrazol-1-yl)-,(42S)-rapamycin (Zotarolimus), 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]rapamycin (temsirolimus), and tacrolimus. 
     
     
         3 . The composition of  claim 1 , wherein the mTOR inhibitor comprises rapamycin. 
     
     
         4 . The composition of  claim 1 , wherein the molar ratio of the polypeptide to the phospholipid is in the range of from about 1:1 to about 1:50. 
     
     
         5 . The composition of  claim 1 , wherein the molar ratio of the polypeptide to the phospholipid is in the range of from about 1:1: to about 1:10. 
     
     
         6 . The composition of  claim 1 , wherein the mass ratio of the polypeptide to the phospholipid is in the range of from about 15:1 to about 3:10. 
     
     
         7 . The composition of  claim 1 , wherein the polypeptide comprises at least 25 contiguous amino acids of SEQ ID NO: 2. 
     
     
         8 . The composition of  claim 1 , wherein the polypeptide comprises an amino acid sequence at least 85% identical to the entire length of SEQ ID NO: 2. 
     
     
         9 . The composition of  claim 1 , wherein the polypeptide comprises an amino acid sequence at least 95% identical to the entire length of SEQ ID NO: 2. 
     
     
         10 . The composition of  claim 1 , wherein the polypeptide comprises an amino acid sequence at least 99% identical to the entire length of SEQ ID NO: 2. 
     
     
         11 . The composition of  claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         12 . The composition of  claim 1 , wherein the nanovesicle has a diameter in the range of from about 10 nm to about 800 nm. 
     
     
         13 . A cell comprising the composition of  claim 1 , wherein the cell is selected from the group consisting of: bacteria; yeast; mouse cell; rat cell, cat cell, dog cell, monkey cell, human cell, archael cell, insect cell, plan cell, algal cell, fungal cell, amphibian cell, reptile cell, worm cell, and animal cell culture lines. 
     
     
         14 . A composition resulting by ingestion in a composition of  claim 1 . 
     
     
         15 . A kit for preparing a cancer treatment comprising:
 a first container housing a saposin C-related polypeptide and a phospholipid;   a second container housing a mTOR inhibitor; and   a third container housing a pharmaceutically-acceptable carrier, diluent, or excipient.   
     
     
         16 . A kit of  claim 15 , wherein the saposin C-related polypeptide comprises an amino acid sequence at least 75% identical to the entire length of SEQ ID NO: 2. 
     
     
         17 . A kit of  claim 15 , wherein the mTOR inhibitor comprises a rapamycin compound.