Abstract: The present disclosure includes biocompatible, nanocomposite hydrogel compositions and vaccines, where the compositions and vaccines include a biocompatible hydrogel material, a plurality of immune stimulating cytokines, such as CXCL9, and a plurality of nano liposomes loaded with mRNA molecules corresponding to a target antigen, such as for a condition to be treated. This disclosure also includes methods of making the biocompatible, nanocomposite hydrogel compositions and vaccines as well as methods of using the vaccines of the present disclosure to treat and/or prevent a disease in a subject.

Abstract: Provided herein is a method of improving sensitivity of a tumor to a host immune response, the method comprising administering to a subject in need thereof a Type I interferon and an immune checkpoint inhibitor, thereby increasing sensitivity of the tumor to a host immune response.

Abstract: The present disclosure provides methods of increasing sensitivity of a tumor to treatment with an immune checkpoint inhibitor (ICI) in a subject and methods of treating a subject with an immune checkpoint inhibitor (ICI)-resistant tumor. The methods comprise administering to the subject a composition comprising a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer. Also provided are methods of increasing the number of activated plasmacytoid dendritic cells (pDCs) in a subject in need thereof, comprising administering to the subject a composition comprising a nanoparticle comprising a positivelycharged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer.

Abstract: The present disclosure provides a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, wherein the nanoparticle comprises RNA molecules encoding a SARS-CoV-2 protein. Methods of making such nanoparticles are further provided herein. Additionally, related cells, populations of cells, pharmaceutical compositions comprising the presently disclosed nanoparticles are provided. Methods of increasing an immune response against a tumor in a subject, methods of delivering RNA molecules to an intra-tumoral microenvironment, lymph node, and/or a reticuloendothelial organ in a subject, and methods of treating a subject with a disease are furthermore provided.

Abstract: Provided herein are compositions comprising a liposome comprising ribonucleic acid (RNA) molecules and a cationic lipid, wherein the RNA molecules bind to or encode an epitope of a nucleic acid encoding a fusion protein expressed by a tumor. The disclosure also provides a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer, and nucleic acid molecules in the nucleic acid layers comprise a sequence of a nucleic acid molecule expressed by slow-cycling cells (SCCs). Also provided herein re methods of making a nanoparticle and methods of increasing an immune response against a tumor in a subject. Methods of treating a subject with a disease are provided herein.

Abstract: The present disclosure provides a nanoparticle comprising a positively-charged surface and an interior comprising (i) a core and (ii) at least two nucleic acid layers, wherein each nucleic acid layer is positioned between a cationic lipid bilayer. Methods of making such nanoparticles are further provided herein. Additionally, related cells, populations of cells, pharmaceutical compositions comprising the presently disclosed nanoparticles are provided. Methods of increasing an immune response against a tumor in a subject, methods of delivering RNA molecules to an intra-tumoral microenvironment, lymph node, and/or a reticuloendothelial organ in a subject, and methods of treating a subject with a disease are furthermore provided.

Abstract: Provided herein are compositions comprising a liposome comprising RNA molecules and a cationic lipid, wherein the RNA molecules encode at least one MHC Class II epitope of a mutant Histone 3 (H3) protein comprising a K27M mutation and optionally at least one MHC Class I epitope of the mutant H3 protein. In exemplary embodiments, the RNA molecules comprise a sequence of SEQ ID NO: 12 or 14. Methods of increasing central memory T cells, increasing an immune response, or treating a diffuse midline glioma (DMG), in a subject are provided herein. In exemplary embodiments, the methods comprise administering to the subject the compositions provided herein.

Abstract: A vaccine composition for enhancing in a subject to whom the composition is administered, a production of antibodies against a disialoganglioside GD3 and/or GD2 is provided in one embodiment. The composition includes, in an embodiment, a liposome including an effective amount of disialoganglioside GD3 and/or GD2 to stimulate or enhance antibody production in the subject; and an effective amount of an adjuvant comprising monophosphory 1 lipid A (MPL). In one example, the vaccine composition may be administered to the subject in conjunction with a chemotherapy.

Abstract: The present disclosure provides compositions comprising a liposome comprising a cationic lipid and nucleic acid molecules comprising a sequence of a nucleic acid molecule expressed by slow-cycling cells (SCCs). The present disclosure also provides methods of preparing an anti-tumor liposome composition. In exemplary embodiments, the method comprises (a) isolating SCCs from a mixed tumor cell population in accordance with any one of the presently disclosed in vitro method of isolating SCCs from a mixed tumor cell population, (b) extracting nucleic acid molecules from the isolated SCCs, and (c) mixing the nucleic acid molecules with a cationic lipid to make an anti-tumor liposome composition. The method of preparing an anti-tumor liposome composition in alternative embodiments comprises mixing at least one SCC transcriptome nucleic acid molecule as described herein with a cationic lipid to make an anti-tumor liposome composition. Tumor treatment methods are furthermore provided by the present disclosure.

Abstract: The present disclosure provides methods of increasing sensitivity of a tumor to treatment with an immune checkpoint inhibitor (ICI) in a subject and methods of treating a subject with an immune checkpoint inhibitor (ICI)-resistant tumor. The methods comprise administering to the subject a composition comprising a liposome comprising a cationic lipid and mRNA molecules, wherein the liposome is systemically administered to the subject. Also provided are methods of increasing the number of activated plasmacytoid dendritic cells (pDCs) in a subject in need thereof, comprising administering to the subject a composition comprising a liposome comprising a cationic lipid and mRNA molecules, wherein the liposome is systemically administered to the subject. Combination therapy with anti-PD-L1 mAb. Related methods of treatment and methods of preparing a dendritic cell vaccine are additionally provided.

Abstract: Provided herein is a liposome comprising ribonucleic acid (RNA) molecules, a lipid mixture comprising DOTAP and cholesterol, and iron oxide nanoparticles (IONPs). Also provided herein is a liposome comprising ribonucleic acid (RNA) molecules and a lipid mixture comprising DOTAP and cholesterol, wherein the DOTAP and cholesterol are present in the lipid mixture at a DOTAP:cholesterol ratio of about 3:1 by mass. Related cells comprising the liposome, populations of cells, and compositions are also provided. Methods of making a liposome and methods of using the liposome are further provided.