Provided herein are isolated anaplastic lymphoma kinase (ALK) peptides that are fragments of the cytoplasmic portion of an ALK protein shared by cancers having an ALK rearrangement and cancers expressing the ALK protein, that bind a human leukocyte antigen (HLA), and elicit an immune response against one or more ALK-positive cancers. Also provided are isolated ALK peptides that are modified with an amphiphilic conjugate to increase T-cell expansion and greatly enhance anti-tumor efficacy. The invention also provides polynucleotides encoding isolated ALK peptides, vaccines comprising an isolated ALK peptide or polynucleotide, immunogenic compositions thereof, and kits for administering the same. Methods of treatment and methods of generating an immune response in a subject by administering the ALK-specific peptide antigens, immunogens, vaccines, or immunogenic compositions thereof are provided.

Provided herein are isolated anaplastic lymphoma kinase (ALK) peptides that are fragments of the cytoplasmic portion of an ALK protein shared by cancers having an ALK rearrangement and cancers expressing the ALK protein, that bind a human leukocyte antigen (HLA), and elicit an immune response against one or more ALK-positive cancers. Also provided are isolated ALK peptides that are modified with an amphiphilic conjugate to increase T-cell expansion and greatly enhance anti-tumor efficacy. The invention also provides polynucleotides encoding isolated ALK peptides, vaccines comprising an isolated ALK peptide or polynucleotide, immunogenic compositions thereof, and kits for administering the same. Methods of treatment and methods of generating an immune response in a subject by administering the ALK-specific peptide antigens, immunogens, vaccines, or immunogenic compositions thereof are provided.

The present disclosure relates to a tumor specific neoantigenic peptide, wherein said peptide (i) is encoded by a part of an (ORF) sequence from an unannotated transcript which transcription is positively regulated by an aberrant fusion protein, and (ii) is expressed at a higher level or frequency in a sample from said tumor compared to normal tissue sample. The present disclosure also relates to vaccine or immunogenic composition, antibodies and immune cells derived thereof and their use in therapy of cancer.

Provided herein, inter alia, are compositions for the modulation of epithelium function, the compositions comprising EphrinA3 protein or EphrinA2 protein, fusions thereof, fragments thereof, or oligonucleotides encoding the same. Also provided are methods for modulating epithelium function, the methods comprising administration of compositions provided herein, including embodiments thereof.

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.

The present invention relates to cancer therapy, in particular cancer immunotherapy. In particular, the present invention relates to methods and products for treating cancer by administration of specific fusion polypeptides or nucleic acids encoding such fusion polypeptides.

An immunotherapeutic mRNA vaccine comprises a first translation unit comprising a secretable first fusion protein comprising a co-stimulatory molecule fused to a first TAA, adapted to generate a first TAA specific adaptive immune response by way of a first immunostimulatory pathway. The immunotherapeutic mRNA vaccine also comprises a second translation unit comprising a non-secretable second fusion protein comprising an identical co-stimulatory molecule fused to a second TAA identical to the first TAA, adapted to generate a second TAA specific adaptive immune response by way of a second immunostimulatory pathway, whereby the at least two immune response interact at one or more locations downstream to amplify the first TAA specific adaptive immune response.

A vector harboring nucleic acids encoding a recombinant T cell receptor having antigenic specificity for a DnaJ heat shock protein family member B1-protein kinase cAMP-activated catalytic subunit alpha (DNAJB1-PRKACA) fusion protein is provided, as are host cells and a method for treating fibrolamellar hepatocellular carcinoma with the vector.

The invention provides methods of detecting a sequence modification (e.g., a genetic fusion or deletion) associated with cancer development that results in expression of a neoantigen. The neoepitope serves as the basis for manufacture of a vaccine, which is administered to a subject to induce an immune response against those cells producing the neoantigen.

A vector harboring nucleic acids encoding a recombinant T cell receptor having antigenic specificity for a DnaJ heat shock protein family member B1-protein kinase cAMP-activated catalytic subunit alpha (DNAJB1-PRKACA) fusion protein is provided, as are host cells and a method for treating fibrolamellar hepatocellular carcinoma with the vector.