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.

Described herein are single chain trimer (SCT) polypeptides comprising or consisting essentially of a target peptide, a first linker, at least a portion of a beta-2 microglobulin domain, a second linker, and at least a portion of a major histocompatibility complex (MHC) I alpha chain, or pharmaceutically acceptable derivatives thereof. The SCT polypeptides may further include a leader peptide, e.g., a PHO5, SUC2, app8, or HLA A2 leader sequence at the N-terminus of the target peptide. Further described herein are polypeptide compositions comprising or consisting essentially of a first polypeptide comprising a target peptide, and a second polypeptide comprising at least a portion of a beta-2 microglobulin domain, a second linker, and at least a portion of a major histocompatibility complex (MHC) I alpha chain, a third linker, and a tether peptide, or pharmaceutically acceptable derivatives thereof. The first polypeptide and/or the second polypeptide may further include a leader peptide, e.g., a PHO5, SUC2, app8, or HLA A2 leader sequence. The present disclosure also includes associated kits, methods, compositions, nucleotides, cells, and uses thereof.

Provided herein are compositions and methods related to the treatment of an autoimmune disease in a subject.

Disclosed herein are minimal arrestin domain containing protein 1 (ARRDC1) constructs, which drive the formation of ARRDC1-mediated microvesicles (ARMMs). These vesicles can be harnessed to package and deliver a variety of molecular cargos such as small molecules, nucleic acids, and proteins. An example of such cargo is the genome editor Cas9.

Disclosed are chimeric stimulatory receptors (CSRs), cell compositions comprising CSRs, methods of making and methods of using same for the treatment of a disease or disorder in a subject.

The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide, an epitope-presenting peptide, and class I MHC polypeptides. 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.

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.

A nucleic acid molecule comprising a nucleotide sequence encoding an inhibitory chimeric antigen receptor (iCAR) capable of preventing or attenuating undesired activation of an effector immune cell, wherein the iCAR comprises an extracellular domain that specifically binds to a single allelic variant of a polymorphic cell surface epitope absent from mammalian tumor cells due to loss of heterozygosity (LOH) but present at least on all cells of related mammalian normal tissue; and an intracellular domain comprising at least one signal transduction element that inhibits an effector immune cell is provided. Vectors and transduced effector immune cells comprising the nucleic acid molecule and methods for treatment of cancer comprising administering the transduced effector immune cells are further provided.

The present invention relates to a nucleic acid molecule, a vector, a host cell, or a protein or peptide, or any combination thereof for use in a method of increasing efficiency of embryonic implantation in an in vitro fertilization programme, (I) wherein the at least one nucleic acid molecule is selected from nucleic acid molecules (a) encoding a polypeptide comprising or consisting of the amino acid sequence of any one of SEQ ID NOs 1 to 17, (b) comprising or consisting of the nucleotide sequence of any one of SEQ ID NOs 18 to 23, (c) encoding a polypeptide which is at least 85% identical, preferably at least 90% identical, and most preferred at least 95% identical to the amino acid sequence of (a), (d) consisting of a nucleotide sequence which is at least 95% identical, preferably at least 96% identical, and most preferred at least 98% identical to the nucleotide sequence of (b), (e) consisting of a nucleotide sequence which is degenerate with respect to the nucleic acid molecule of (d), (f) consisting of a fragment of the nucleic acid molecule of any one of (a) to (e), said fragment comprising at least 150 nucleotides, preferably at least 300 nucleotides, more preferably at least 450 nucleotides, and most preferably at least 600 nucleotides, and (g) corresponding to the nucleic acid molecule of any one of (a) to (f), wherein T is replaced by U, and (II) the vector comprises the nucleic acid molecule of (I); (III) the host cell is transformed, transduced or transfected with the vector of (II); and (IV) the at least one protein or peptide is selected from proteins or peptides being encoded by the nucleic acid molecule of (I); and wherein the method of increasing embryonic implantation efficiency comprises (i) contacting the nucleic acid molecule, vector, host cell, or protein or peptide, or any combination thereof with the unfertilized, fertilized oocyte, and/or preimplantation embryo prior to the transfer of the fertilized oocyte or preimplantation embryo to the uterus; or (ii) contacting the nucleic acid molecule, vector, host cell, or protein or peptide, or any combination thereof with the uterus prior to, simultaneously with and/or after the transfer of the fertilized oocyte or preimplantation embryo to the uterus; or (iii) systemically administering the nucleic acid molecule, vector, host cell, or protein or peptide, or any combination prior to, simultaneously with and/or after the transfer of the fertilized oocyte or preimplantation embryo to the uterus, preferably via injection, transdermal and/or vaginal administration.

The present disclosure provides methods for inducing neoepitope-specific CD8+ T cells in an individual or for inducing trafficking of neoepitope-specific CD8+ T cells to a tumor in an individual using an RNA vaccine or using an RNA vaccine in combination with a PD-1 axis binding antagonist. Also provided herein are PD-1 axis binding antagonists and RNA vaccines that include one or more polynucleotides encoding one or more neoepitopes resulting from cancer-specific somatic mutations present in a tumor specimen obtained from the individual for use in methods of inducing neoepitope-specific CD8+ T cells in an individual or for inducing trafficking of neoepitope-specific CD8+ T cells to a tumor in an individual.