The present invention relates to: a composition for delivering a viral antigen-derived CD8.sup.+ T cell antigen epitope or a peptide comprising same to the cytoplasm of a target cell to thereby present the epitope or peptide to major histocompatibility complex class I (MHC-1), which is an antigen-presenting molecule on the cell surface; a composition comprising same; and a use thereof.

The present disclosure provides T-cell modulatory multi-merit polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. 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 application relates to vaccine compositions comprising an amphipathic compound, a neoantigen and a hydrophobic carrier. Further described are methods and use of the vaccine composition for inducing an antibody immune response and/or a cell-mediated immune response to the neoantigen, as well as methods and uses of the vaccine compositions in the treatment of cancer.

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Immunotherapeutic methods and compositions are contemplated in which neoepitopes and/or tumor associated antigens are delivered to dendritic cells via an adenoviral expression system that targets MHC-I and/or MHC-II presentation systems and that further provides one or more recombinant peptides to stimulate T cell activation and interfere with checkpoint inhibition. Treatment is further supported by transfusion of NK cells, which may be modified to have a high affinity CD16 receptor and/or a chimeric antigen receptor that binds to one or more neoepitopes and/or tumor associated antigens.

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.

Adaptive immune responses rely on the ability of cytotoxic T cells to identify and eliminate cells displaying disease-specific antigens on human leukocyte antigen (HLA) class I molecules. Investigations into antigen processing and display have immense implications in human health, disease and therapy. To extend understanding of the rules governing antigen processing and presentation, immunopurified peptides from B cells, each expressing a single HLA class I allele, were profiled. A resource dataset containing thousands of peptides bound to distinct class I HLA-A, -B, and -C alleles was generated by implementing a novel allele-specific database search strategy. Applicants discovered new binding motifs, established the role of gene expression in peptide presentation and improved prediction of HLA-peptide binding by using these data to train machine-learning models. These streamlined experimental and analytic workflows enable direct identification and analysis of endogenously processed and presented antigens.

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 provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

The invention relates to concatemeric peptide epitope RNAs, as well as methods and compositions thereof. mRNA vaccines are also provided according to the invention, including cancer vaccines.