Disclosed is a T cell receptor (TCR) having antigenic specificity for an HLA-A2-restricted epitope of human papillomavirus (HPV) 16 E6, E6.sub.29-38. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, and populations of cells are also provided. Antibodies, or an antigen binding portion thereof, and pharmaceutical compositions relating to the TCRs of the invention are also provided. Also disclosed are methods of detecting the presence of a condition in a mammal and methods of treating or preventing a condition in a mammal, wherein the condition is cancer, HPV 16 infection, or HPV-positive premalignancy.

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.

Provided are SLC45A2 peptides that bind to MHC I (HLA-A2) on melanoma cells or other antigen-presenting cells and are recognized by T-cell receptors on T cells. The SLC45 A2 peptides may be therapeutically used to treat a cancer, such as a cutaneous melanoma, uveal melanoma, a mucosal melanoma, or a metastatic melanoma. Methods for expanding a population of T cells that target SLC45A2 are also provided.

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

Compositions comprising donor cells, acceptor cells, and methods involving the same are described herein. In some embodiments, the donor cell comprises a T cell receptor (TCR) and a cargo, and the acceptor cell comprises an MHC. In some embodiments, the TCR facilitates transfer of the cargo to the acceptor cell. In some embodiments, the donor cell comprises a chimeric antigen receptor (CAR) and a cargo, and the acceptor cell comprises an antigen bound by the CAR. In some embodiments, the CAR facilitates transfer of the cargo to the acceptor cell.

The application relates to biological components, methods, systems, and kits for modulating immune responses. The disclosed biological components include genetically modified cells comprising an inserted exogenous sequence in a major histocompatibility complex (MHC)-associated gene. The inserted exogenous sequence encodes a peptide and the genetically modified cells express a fusion protein comprising the peptide and at least a portion of the polypeptide encoded by the MHC-associated gene to form a modified MHC complex. The genetically modified cells may present the peptide as an antigen associated with the MHC complex and may be utilized in methods for modulating T cell activity, inducing an immune response, and inducing a tolerogenic response. As such, the disclosed biological components, methods, systems, and kits may be utilized in order to treat and/or prevent a disease or disorder in a subject in need thereof and to screen and validate clinically relevant 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 an isolated cell composition suitable for adoptive immunotherapy, as well as methods of manufacturing the cell compositions and methods of treatment with the cell compositions. The composition comprises, in a pharmaceutically acceptable carrier, at least about 10.sup.6 CD8+ T cells specific for target peptide antigen(s). In various embodiments, the composition is predominately CD8+ T cells, and at least about 20% of T cells in the composition exhibit a central or effector memory phenotype, providing for a robust and durable adoptive therapy from a natural T cell repertoire that has undergone natural selection.

Non-genetically engineered mammalian cells modified by sortase-mediated conjugation of an agent thereto are provided. Methods of conjugating agents to nongenetically engineered mammalian cells using sortase are provided. Methods of using the cells, e.g. a method of modulating an immune response of a subject to an entity of interest, a method of neutralizing a substance in the body of a subject, a method of treating a subject in need of treatment for deficiency of a protein, and a method of treating a subject in need of treatment for a disease, are provided.

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.