The present invention discloses a process for manufacturing a formulation comprising a drug substance, said drug substance comprising a recombinant Listeria comprising a human papilloma virus (HPV) antigen fused to a Listeriolysin O (LLO) protein fragment. The invention further discloses methods of using treating, protecting against, and inducing an immune response against cervical cancer comprising administration of the recombinant Listeria strain. The present invention also provides methods for inducing an anti-E7 CTL response in a human subject and treating HPV-mediated diseases, disorders, and symptoms, comprising administration of the recombinant Listeria strain.

The present invention provides DNA vaccines for the treatment of allergies. The vaccines comprise the coding sequence for one or more allergenic epitopes, and preferably the full protein sequence, of the allergenic protein from which the epitope(s) is derived, fused inframe with the lumenal domain of the lysosomal associated membrane protein (LAMP) and the targeting sequence of LAMP. The vaccines allow for presentation of properly configured three dimensional epitopes for production of an immune response. The vaccines can be multivalent molecules, and/or can be provided as part of a multivalent vaccine containing two or more DNA constructs.

Provided herein is a construct comprising, in combination: an EphA3, EphA2 and/or EphB2 binding ligand; and at least one effector molecule. In some embodiments, the at least one effector molecule comprises a therapeutic agent, a nanoparticle, a detectable group, a lipid, or a liposome. In some embodiments, the construct is a fusion protein and/or a covalent conjugate. Further provided is a construct comprising, in combination: a ligand that binds to EphA2, EphA3 and/or EphB2; a ligand that binds to IL-13Ra2; and at least one effector molecule. Also provided are methods of use thereof for treating cancer.

Vaccine design, polycistronic vaccine constructs, compositions, and methods comprising nucleic acids (DNA, RNA), peptides, proteins and derivatives thereof, including cells and cell-lines, for enhanced antigen-specific vaccination.

Disclosed are extracellular vesicles comprising an engineered targeting protein for targeting the extracellular vesicles to target cells. The targeting protein is a fusion protein that includes a ligand, an engineered glycosylation site, and an exosome-targeting domain. Exemplary extracellular vesicles may include but are not limited to exosomes.

The present invention relates to (isolated) recombinant proteins, also referred to as improved MAT (iMAT) molecules, comprising at least one translocation module, at least one targeting module and at least one antigen module, wherein at least one cysteine residue is substituted with a different amino acid residue. Such iMAT molecules are useful specifically as vaccines, e.g., for therapy and/or prevention of allergies and/or infectious diseases and/or prevention of transmission of infectious diseases in equines. The present invention further relates to nucleic acids encoding such iMAT molecules, corresponding vectors and primary cells or cell lines.

The invention provides chimeric proteins and nucleic acids encoding these which can be used to generate vaccines against selected antigens. In one aspect, a chimeric protein comprises an antigen sequence and a domain for trafficking the protein to an endosomal compartment, irrespective of whether the antigen is derived from a membrane or non-membrane protein. In one preferred aspect, the trafficking domain comprises a lumenal domain of a LAMP polypeptide. Alternatively, or additionally, the chimeric protein comprises a trafficking domain of an endocytic receptor (e.g., such as DEC-205 or gp200-MR6). The vaccines (DNA, RNA or protein) can be used to modulate or enhance an immune response against any kind of antigen. In one preferred aspect, the invention provides a method for treating a patient with cancer by providing a chimeric protein comprising a cancer-specific antigen or a nucleic acid encoding the protein to the patient.

Provided herein is a construct comprising, in combination: an EphA3, EphA2 and/or EphB2 binding ligand; and at least one effector molecule. In some embodiments, the at least one effector molecule comprises a therapeutic agent, a nanoparticle, a detectable group, a lipid, or a liposome. In some embodiments, the construct is a fusion protein and/or a covalent conjugate. Further provided is a construct comprising in combination: a ligand that binds to EphA2, EphA3 and/or EphB2; a ligand that binds to IL-13R2; and at least one effector molecule. Also provided are methods of use thereof for treating cancer.

Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

The present invention provides further improved compositions and methods for efficient lysosomal targeting based on the GILT technology. Among other things, the present invention provides methods and compositions for targeting lysosomal enzymes to lysosomes using furin-resistant lysosomal targeting peptides. The present invention also provides methods and compositions for targeting lysosomal enzymes to lysosomes using a lysosomal targeting peptide that has reduced or diminished binding affinity for the insulin receptor.