The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to artificial antigen presenting cell (aAPC) scaffolds to provide cells with specific functional stimulation to obtain phenotypic and functional properties ideal to mediate tumor regression or viral clearance. In particular, the scaffolds of the present invention comprise antigens, such as peptide-MHC (pMHC) class I molecules, and specific combinations of cytokines and co-stimulatory molecules to allow effective expansion and functional stimulation of specific T cells.

The invention provides lipid A mimics in which one or both of the sugar residues of a natural lipid A disaccharide backbone has been replaced with an aromatic group. These lipid A mimics may further differ from a natural lipid A molecule with respect to other structural characteristics, such as, a different number of phosphate groups present, changes in the number, structure and location of lipid chains and/or changes in the spacing and linkage of the sugar residues (or their aromatic replacements). The lipid A mimics may be lipid A agonists and as such may be useful as immunostimulatory agents in inducing or patenting an antibody and/or cell-mediated immune response, or may be lipid A antagonists and as such may be useful in treating or preventing a lipopolysaccharide (LPS)/lipid A-mediated disease or disorder. Also provided are methods for preparing the lipid A mimics.

The present disclosure provides variant immunomodulatory polypeptides, and fusion polypeptides comprising the variant immunomodulatory peptides. The present disclosure provides T-cell modulatory multimeric polypeptides, and compositions comprising same, where the T-cell modulatory multimeric polypeptides comprise a variant immunomodulatory polypeptide of the present disclosure. The present disclosure provides nucleic acids comprising nucleotide sequences encoding the T-cell modulatory multimeric polypeptides, and host cells comprising the nucleic acids. The present disclosure provides methods of modulating the activity of a T cell; the methods comprise contacting the T cell with a T-cell modulatory multimeric polypeptide of the present disclosure.

The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide that exhibits reduced binding affinity to a cognate co-immunomodulatory polypeptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.

The present disclosure provides Multimeric Antigen-Presenting Polypeptides (MAPPs) for the presentation of epitopes in the context of a class II MHC receptor. The present disclosure provides nucleic acids comprising nucleotide sequences encoding those MAPPs, as well as cells genetically modified with the nucleic acids encoding the MAPPs. MAPPs are useful for selectively modulating activity of T cells having T cell receptors that recognize the antigens. Thus, the present disclosure provides compositions and methods for modulating the activity of T cells, as well as compositions and methods for treating persons who have diseases and/or disorders including cancers, autoimmune diseases and/or allergies.

The present invention relates to the construction and application of a fusion protein vaccine platform. The present invention provides a vaccine, comprising a fusion protein containing an interferon-target antigen-immunoglobulin Fc region (or antibody) and a Th cell helper epitope. The present invention also relates to use of a fusion protein containing an interferon-target antigen-immunoglobulin Fc region (or antibody) and a Th cell helper epitope in the preparation of prophylactic or therapeutic compositions. The vaccine of the present invention can be produced by eukaryotic cell expression systems to prepare wild-type and various mutant antigen vaccines, and vaccination by means of subcutaneous/muscular or nasal or other routes can lead to a strong immune response to a body. The vaccine of the present invention can be used as a prophylactic or therapeutic vaccine.

Compositions comprising an MHC ligand peptide covalently attached to an MHC class II molecule are provided herein. In some compositions, the MHC ligand peptide is covalently attached to the MHC class II molecule by a peptide linker, wherein the MHC ligand peptide or the peptide linker comprises a first cysteine, wherein the MHC class II a chain or a portion thereof or the MHC class II β chain or a portion thereof comprises a second cysteine, and wherein the first cysteine and the second cysteine form a disulfide bond such that the MHC ligand peptide is bound in a peptide-binding groove formed by the MHC class II a chain or the portion thereof and the MHC class II β chain or the portion thereof. Also provided are nucleic acids encoding such compositions and methods for using such compositions to elicit an immune response in a subject.

Provided are peptide-MHC class I and class II molecules having improved stability and high potency, and that can be produced in high yield. Also provided are receptor-signaling nanoparticles comprising the improved peptide-MHC molecules.

This disclosure relates to immunogenic peptides that are specific to B-cell maturation antigen (BCMA) and Transmembrane activator and CAML interactor (TACI), and methods of use thereof.