The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

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 disclosure is directed, in some embodiments, to methods and compositions of comprising a cell having a non-internalizing receptor, and a nanoparticle surface-modified with a ligand that binds to the non-internalizing receptor.

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 invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The present invention provides a fusion protein, comprising a chemokine polypeptide, which is a chemokine or a receptor binding domain thereof; and a cytokine polypeptide connected to said chemokine polypeptide, which is an interleukin, a TNF-superfamily cytokine or a receptor-binding domain thereof; wherein the chemokine polypeptide and the cytokine polypeptide have a common target cell, and the fusion protein has an improved chemokine activity as compared to the chemokine polypeptide, and an improved cytokine activity as compared to the cytokine polypeptide.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The invention relates to prophylaxis and therapy of cancer. In particular there is provided a protein Tryptophan2,3-di-oxygenase (TDO) or peptide fragments here of that are capable of eliciting anti-cancer immune responses. Specifically, the invention relates to the use of TDO or peptides derived thereof or TDO specific T-cells for treatment of cancer. The invention thus relates to an anti-cancer vaccine which optionally may be used in combination with other immunotherapies and to TDO specific T-cells adoptively transferred or induced in vivo by vaccination as a treatment of cancer. It is an aspect of the invention that the medicaments herein provided may be used in combination with cancer chemotherapy treatment. A further aspect relates to the prophylaxis and therapy of infections by the same means as described above.

This document provides methods and materials related to using monovalent anti-CD3 antibodies (e.g., monovalent anti-CD3 Fab fragments) as adjuvants to increase the immune response produced against an antigen (e.g., a tumor associated antigen). For example, vaccine compositions containing monovalent anti-CD3γε Fab fragments in combination with tumor associated antigens (e.g., tumor associated antigens having little or no immunogenicity in the absence of monovalent anti-CD3γε Fab fragments) alone or in combination with adjuvants for signals two and/or three required for full activation of T cell immune function, as well as methods and materials for using monovalent anti-CD3γε Fab fragments to increase the immune response produced against an antigen (e.g., a tumor associated antigen) within a mammal (e.g., a human) are provided.

Disclosed are biocompatible core/shell compositions suitable for the delivery of populations of mRNA molecules to mammalian cells. The disclosed core-shell structured multicomponent compositions are optimized for the delivery of mRNAs encoding one or more cancer- or tumor-specific antigens to a population of antigen presenting cells, including, for example, human dendritic cells, macrophages and B cells. Also disclosed are methods for use of these compositions as therapeutic cancer vaccines.