Lipid vesicle compositions and methods of use

Abstract

The invention provides delivery systems comprised of stabilized multilamellar vesicles, as well as compositions, methods of synthesis, and methods of use thereof. The stabilized multilamellar vesicles comprise terminal-cysteine-bearing antigens or cysteine-modified antigens, at their surface and/or internally.

1 - 62 . (canceled) 
     
     
         63 . A multilamellar lipid vesicle comprising at least one terminal-cysteine-bearing antigen, and having covalent crosslinks between lipid bilayers, wherein at least two lipid bilayers in the multilamellar lipid vesicle are covalently crosslinked to each other through headgroups that react with covalent crosslinkers to form the covalent crosslinks between lipid bilayers, and wherein the terminal-cysteine bearing antigen is a cancer antigen. 
     
     
         64 . The multilamellar lipid vesicle of  claim 63 , wherein the cancer antigen is MART-1/Melan-A, gp100, adenosine deaminase-binding protein (ADAbp), FAP, cyclophilin b, colorectal associated antigen (CRC)-0017-1A/GA733, carcinoembryonic antigen (CEA), CAP-1, CAP-2, etv6, AML1, prostate specific antigen (PSA), PSA-1, PSA-2, PSA-3, prostate-specific membrane antigen (PSMA), T cell receptor/CD3-zeta chain, CD20, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A5, MAGE-A6, MAGE-A7, MAGE-A8, MAGE-A9, MAGE-A10, MAGE-A11, MAGE-A12, MAGE-Xp2 (MAGE-B2), MAGE-Xp3 (MAGE-B3), MAGE-Xp4 (MAGE-B4), MAGE-C1, MAGE-C2, MAGE-C3, MAGE-C4, MAGE-C5), GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE-7, GAGE-8, GAGE-9, BAGE, RAGE, LAGE-1, NAG, GnT-V, MUM-1, CDK4, tyrosinase, p53, a MUC family protein, HER2/neu, p21ras, RCAS1, alpha-fetoprotein, E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, p120ctn, gp100Pmel117, PRAME, NY-ESO-1, cdc27, adenomatous polyposis  coli  protein (APC), fodrin, Connexin 37, Ig-idiotype, p15, gp75, GM2 ganglioside, GD2 ganglioside, a human papilloma virus protein, a Smad family tumor antigen, 1mp-1, P1A, EBV-encoded nuclear antigen (EBNA)-1, brain glycogen phosphorylase, SSX-1, SSX-2 (HOM-MEL-40), SSX-1, SSX-4, SSX-5, SCP-1, CT-7, or c-erbB-2. 
     
     
         65 . The multilamellar lipid vesicle of  claim 63 , wherein the multilamellar lipid vesicle comprises a first terminal-cysteine-bearing cancer antigen and a second terminal-cysteine-bearing cancer antigen, wherein the first and the second terminal-cysteine-bearing cancer antigens are different. 
     
     
         66 . The multilamellar lipid vesicle of  claim 63 , wherein the vesicle comprises phosphocholine and/or phosphoglycerol. 
     
     
         67 . The multilamellar lipid vesicle of  claim 63 , wherein the vesicle comprises a maleimide functionalized lipid. 
     
     
         68 . The multilamellar lipid vesicle of  claim 63 , wherein the cancer antigen is present on the surface of the vesicle, encapsulated between lipid bilayers, and/or is present in the core of the vesicle. 
     
     
         69 . The multilamellar lipid vesicle of  claim 63 , wherein the vesicle is surface-conjugated to polyethylene glycol (PEG). 
     
     
         70 . The multilamellar lipid vesicle of  claim 63 , wherein said terminal-cysteine-bearing antigen is a cysteine-modified antigen. 
     
     
         71 . The multilamellar lipid vesicle of  claim 63 , further comprising an adjuvant. 
     
     
         72 . A composition comprising multilamellar lipid vesicles of  claim 63 . 
     
     
         73 . The composition of  claim 72 , further comprising a pharmaceutically acceptable carrier. 
     
     
         74 . The composition of  claim 72 , further comprising an adjuvant.