Cationic liposomes for cancer immunotherapy

Abstract

Disclosed are positively-charged, cytotoxic nanoparticle compositions comprising immune modulators (such as the toll-like receptor (TLR)-4 ligand, monophosphoryl lipid (MPL)-A), and Interleukin (IL)-12)), which exhibit enhanced uptake by mammalian cancer cells, and cause increased cancer cell death and/or an increased release of cancer antigens following direct injection to populations of cancer or tumor cells. Also disclosed are nanoparticle-vectored, immunomodulatory compositions that stimulate antigen presenting immune cells and T cells, and support the development of anti-cancer immunity in mammalian hosts. The disclosed cationic liposomes represent an important advance in the area of cancer immunotherapeutics.

1 - 21 . (canceled) 
     
     
         22 . A method for providing an antigen to a mammalian cell, comprising administering to a mammalian subject in need thereof, an effective amount of a cationic liposomal nanoparticle composition comprising: (i) a body, (ii) at least one outer surface; and (iii) at least one reservoir inside the body, wherein the nanoparticle comprises one or more toll-like receptor ligands (TLR-L), one or more distinct lipids, and an interleukin or other Type I cytokine on or about its outer surface. 
     
     
         23 . The method of  claim 22 , wherein the mammalian subject is at risk for developing, is suspected of having, or is diagnosed with, a tumor or a cancer. 
     
     
         24 . The method of  claim 23 , wherein the mammalian subject is a human that has been diagnosed with breast cancer. 
     
     
         25 . A method of administering a diagnostic, therapeutic, or prophylactic agent to one or more cells, tissues, organs, or systems of a mammalian subject in need thereof, comprising administering to the subject an effective amount of a cationic liposomal nanoparticle composition comprising: (i) a body, (ii) at least one outer surface; and (iii) at least one reservoir inside the body, wherein the nanoparticle comprises one or more toll-like receptor ligands (TLR-L), one or more distinct lipids, and an interleukin or other Type I cytokine on or about its outer surface. 
     
     
         26 . A method of providing long-term protection against cancer recurrence in a human, comprising administering to a human subject in need thereof, an amount of a cationic liposomal nanoparticle composition comprising: (i) a body, (ii) at least one outer surface; and (iii) at least one reservoir inside the body, wherein the nanoparticle comprises one or more toll-like receptor ligands (TLR-L), one or more distinct lipids, and an interleukin or other Type I cytokine on or about its outer surface and for a time effective to provide long-term protection against cancer recurrence. 
     
     
         27 . The method of  claim 23 , wherein the nanoparticle comprises one or more TLR-4 ligands, optionally monophosphoryl lipid A (MPL-A), and Interleukin-12 (IL-12) on or about its outer surface. 
     
     
         28 . The method of  claim 23 , further comprising at least one cellular-targeting moiety comprising a chemical targeting moiety, a physical targeting moiety, a ligand moiety, a ligand targeting moiety, a geometrical targeting moiety, or an imaging agent, a contrast agent, a radiolabel, a chemotherapeutic agent, a targeting agent; or at least one moiety selected from the group consisting of a ligand, a dendrimer, an oligomer, an aptamer, a binding protein, an antibody, an antigen binding fragment thereof, a biomolecule, or any combination thereof. 
     
     
         29 . The method of  claim 23 , wherein the at least one outer surface further comprises one or more dendritic cells, one or more cytokines, or any combination thereof. 
     
     
         30 . The method of  claim 23 , wherein the nanoparticle further comprises one or more antineoplastic agents, one or more other cytotoxic agents, one or more cytostatic agents, or one or more therapeutic or chemotherapeutic agents, or any combination thereof. 
     
     
         31 . The method of  claim 23 , wherein the nanoparticle comprises DOTAP, DPPC, or cholesterol, or any combination thereof. 
     
     
         32 . The method of  claim 25 , wherein the nanoparticle comprises one or more TLR-4 ligands, optionally monophosphoryl lipid A (MPL-A), and Interleukin-12 ( 1 L-12) on or about its outer surface. 
     
     
         33 . The method of  claim 25 , further comprising at least one cellular-targeting moiety comprising a chemical targeting moiety, a physical targeting moiety, a ligand moiety, a ligand targeting moiety, a geometrical targeting moiety, or an imaging agent, a contrast agent, a radiolabel, a chemotherapeutic agent, a targeting agent; or at least one moiety selected from the group consisting of a ligand, a dendrimer, an oligomer, an aptamer, a binding protein, an antibody, an antigen binding fragment thereof, a biomolecule, or any combination thereof. 
     
     
         34 . The method of  claim 25 , wherein the at least one outer surface further comprises one or more dendritic cells, one or more cytokines, or any combination thereof. 
     
     
         35 . The method of  claim 25 , wherein the nanoparticle further comprises one or more antineoplastic agents, one or more other cytotoxic agents, one or more cytostatic agents, or one or more therapeutic or chemotherapeutic agents, or any combination thereof. 
     
     
         36 . The method of  claim 25 , wherein the nanoparticle comprises DOTAP, DPPC, or cholesterol, or any combination thereof. 
     
     
         37 . The method of  claim 26 , wherein the nanoparticle comprises one or more TLR-4 ligands, optionally monophosphoryl lipid A (MPL-A), and Interleukin-12 (IL-12) on or about its outer surface. 
     
     
         38 . The method of  claim 26 , further comprising at least one cellular-targeting moiety comprising a chemical targeting moiety, a physical targeting moiety, a ligand moiety, a ligand targeting moiety, a geometrical targeting moiety, or an imaging agent, a contrast agent, a radiolabel, a chemotherapeutic agent, a targeting agent; or at least one moiety selected from the group consisting of a ligand, a dendrimer, an oligomer, an aptamer, a binding protein, an antibody, an antigen binding fragment thereof, a biomolecule, or any combination thereof. 
     
     
         39 . The method of  claim 26 , wherein the at least one outer surface further comprises one or more dendritic cells, one or more cytokines, or any combination thereof. 
     
     
         40 . The method of  claim 26 . wherein the nanoparticle further comprises one or more antineoplastic agents, one or more other cytotoxic agents, one or more cytostatic agents, or one or more therapeutic or chemotherapeutic agents, or any combination thereof. 
     
     
         41 . The method of  claim 26 , wherein the nanoparticle comprises DOTAP, DPPC, or cholesterol, or any combination thereof.