Stimulation of an immune response by enantiomers of cationic lipids

Abstract

A composition and method for activating immune cells ex-vivo, or inducing an immune response in a subject including a composition comprising at least one chiral cationic lipid. The chiral cationic lipid in one embodiment comprises a nonsteroidal cationic lipid having a structure represented by formula (I); wherein in R1 is a quaternary ammonium group, Y1 is a space chosen from a hydrocarbon chain, an ester, a ketone, and a peptide, C* is a chiral carbon, R2 and R3 are independently chosen from a saturated fatty acid, an unsaturated fatty acid, an ester-linked hydrocarbon, phosphor-diesters, and combination thereof.

1 . A method of enhancing an immunostimulatory effect in an immune system of a mammal to respond prophylactically or therapeutically to an infection,
 said method comprising the step of administering a immunogenic composition to the mammal, wherein the composition comprises a cationic lipid and an antigen,   wherein the antigen consists of T-cell receptor gamma alternate reading frame protein or (TARP) or Mucin 1 (MUC 1).   
     
     
         2 . The method of  claim 1 , wherein the cationic lipid comprises a chiral cationic lipid. 
     
     
         3 . The method of  claim 2 , wherein the chiral cationic lipid comprises 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), N-1-(2,3-dioleoyloxy) propyl-N,N,N-trimethyl ammonium chloride (DOTMA), 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine (DOEPC), and combinations thereof. 
     
     
         4 . The method of  claim 3 , wherein the composition further comprises one or more therapeutic ingredients selected from the group consisting of drug molecules, cytokines, chemokines, polymer complexes and pharmaceutical carriers. 
     
     
         5 . The method of  claim 1 , wherein the antigen consists of TARP and antigenic fragments thereof. 
     
     
         6 . The method of  claim 5 , wherein the composition further comprises a nucleic acid molecule that encodes the amino acid sequence of TARP and antigenic fragments thereof. 
     
     
         7 . The method of  claim 6  wherein the modified to increase its hydrophobicity or wherein the protein domain of the antigen is modified to facilitate purification by adding a C-terminal protein tag that includes a poly-histidine tag and a proteolytic cleavage sequence for removal of the tags. 
     
     
         8 . The method of  claim 1 , wherein the antigens consists of MUC 1 and antigenic fragments thereof. 
     
     
         9 . The method of  claim 8 , wherein the composition further comprises a nucleic acid molecule that encodes an amino acid sequence of MUC 1 and antigenic fragments thereof. 
     
     
         10 . The method of  claim 9 , wherein the antigen is modified to increase its hydrophobicity or wherein the protein domain of the antigen is modified to facilitate purification by adding a C-terminal protein tag that includes a poly-histidine tag and a proteolytic cleavage sequence for removal of the tags. 
     
     
         11 . The method of  claim 1 , wherein the cationic lipid comprises DOTAP. 
     
     
         12 . The method of  claim 11 , wherein the cationic lipid consists of R-DOTAP. 
     
     
         13 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         14 . The method of  claim 1 , wherein the wherein the composition is administered as an aerosol or as a liquid solution for intratumoral, intraarterial, intravenous, intratracheal, intraperitoneal, subcutaneous, or intramuscular administration. 
     
     
         15 . The method of  claim 1 , wherein the immunostimulatory effect includes production of immune system regulatory molecules. 
     
     
         16 . A pharmaceutical composition comprising an immunologically active enantiomer of a cationic lipid component, wherein the cationic lipid component consists of R-DOTAP,
 and an antigen, wherein the antigen consists of T-cell receptor gamma alternate reading frame protein or (TARP) or Mucin 1 (MUC 1),   and wherein the composition is effective to activate an immune system in a patient.   
     
     
         17 . The pharmaceutical composition of  claim 16 , further comprising additional lipids selected from the group consisting of lyso lipids, lysophosphatidylcholine, 1-oleoyl lysophosphatidylcholine, cholesterol, neutral phospholipids, dioleoyl phosphatidyl ethanolamine (DOPE), dioleoyl phosphatidylcholine (DOPC), lipophilic surfactants, Tween-80 and PEG-PE, and combinations thereof. 
     
     
         18 . The pharmaceutical composition of  claim 16 , wherein the antigen consists of TARP, or antigenic fragments thereof. 
     
     
         19 . The pharmaceutical composition of  claim 18 , wherein the composition further comprises a nucleic acid molecule that encodes an amino acid sequence of TARP, or antigenic fragments thereof. 
     
     
         20 . The pharmaceutical composition of  claim 16 , wherein the antigen consists of MUC 1, or antigenic fragments thereof. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the composition further comprises a nucleic acid molecule that encodes an amino acid sequence of MUC 1, or antigenic fragments thereof. 
     
     
         22 . The pharmaceutical composition of  claim 16 , wherein the antigen includes an antigen modified to increase its hydrophobicity.