The present invention relates to methods for the production of heat shock protein complexes for use in vaccine compositions. In particular, there is provided a method for increasing the level and immunogenicity of heat shock protein complexes produced in cells by subjecting the cells to specific stress inducing stimuli. The invention further extends to the use of heat shock protein complexes produced according to the methods of the invention in the preparation of vaccine compositions for the prevention and treatment of infectious diseases and cancerous conditions.

Anti-tumor immune responses to modified self-epitopes. The present invention relates to the use of tumor-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumor and have a modification selected from deimination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer.

A polypeptide encoding a chimeric antigen receptor (CAR) comprising at least one extracellular binding domain that comprises a scFv formed by at least a VH chain and a VL chain specific to an antigen, wherein said extracellular binding domain comprises at least one mAb-specific epitope.

The invention describes a method for preparing a composition comprising tumour cell stress proteins, said method comprising the following steps: providing tumour cells in a culture medium; subjecting the tumour cells under i) to a stress with the result that these cells produce stress proteins in response to the stress; obtaining or recovering stressed tumour cells and/or stress proteins; treating the stressed tumour cells and/or the stress proteins obtained with a molecule or a process capable of rendering the stress proteins immunogenic, preferably a hapten or haptenization. The invention also describes a pharmaceutical composition comprising tumour cell stress proteins and/or tumour cells comprising stress proteins, these stress proteins being rendered immunogenic, and are in particular haptenized, and a pharmaceutically acceptable excipient.

The present invention relates to methods for preparing and using multichaperone-antigen complexes. The present invention uses HOP affinity molecules in affinity methods to isolate multichaperone (multi-HSP)-antigen complexes. Such complexes have use in therapy.

The present application relates generally to genetically modified arenaviruses that are suitable vaccines against neoplastic diseases, such as cancer. The arenaviruses described herein may be suitable for vaccines and/or treatment of neoplastic diseases and/or for the use in immunotherapies. In particular, provided herein are methods and compositions for treating a neoplastic disease by administering a genetically modified arenavirus in combination with an immune checkpoint inhibitor, wherein the arenavirus has been engineered to include a nucleotide sequence encoding a tumor antigen, tumor associated antigen or antigenic fragment thereof.

Anti-tumour immune responses to modified self-epitopes. The present invention relates to the use of tumour-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumour and have a modification selected from deimination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer.

The application provides a polypeptide comprising the sequence SLMTNLAAL (SEQ ID NO: 8), Ser 13 to Leu 21 of amino acid sequence shown in FIG. 1 or SEQ ID No 1, and having HLA-A2 haplotype binding activity, or a polynucleotide encoding said polypeptide. Vaccines containing the polypeptide or polynucleotides encoding the polypeptide are also provided.

The present invention relates to a nucleic acid sequence, comprising or coding for a coding region, encoding at least one peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, at least one histone stem-loop and a poly(A) sequence or a polyadenylation signal. Furthermore the present invention provides the use of the nucleic acid for increasing the expression of said encoded peptide or protein. It also discloses its use for the preparation of a pharmaceutical composition, especially a vaccine, e.g. for use in the treatment of cancer or tumour diseases. The present invention further describes a method for increasing the expression of a peptide or protein comprising a tumour antigen or a fragment, variant or derivative thereof, using the nucleic acid comprising or coding for a histone stem-loop and a poly(A) sequence or a polyadenylation signal.

In some aspects, the invention relates to compositions and methods of generating antigens, wherein the antigen is a biomolecule that is modified by a reactive oxygen species or a reactive nitrogen species. In some aspects, the invention relates to compositions and methods of generating antibodies that bind to biomolecules that have been modified by a reactive oxygen species or a reactive nitrogen species. In some aspects, the invention relates to compositions and methods of generating antibodies that bind to novel epitopes on unmodified biomolecules. In some aspects, the invention relates to the induction of active immunotherapeutic processes (e.g., using preventive or therapeutic vaccines), which may comprise administering neo-antigens generated through methods and compositions described herein.