Embodiments of the disclosure include methods and compositions directed to targeting of cells that express the long form of Bone marrow stromal cell antigen 2 (BST2) protein, including cancer cells that express the long isoform of BST2. In particular embodiments, monoclonal antibodies or functionally active fragments thereof are utilized to target cells that express the long isoform of BST2. The monoclonal antibodies or functionally active fragments thereof may be utilized by themselves or as part of other entities, such as cells or engineered antigen receptors. The disclosure includes methods of treatment, prevention, and/or diagnosis using the encompassed antibodies or functional fragments thereof.

Provided are methods for isolating T-cells with T cell receptors (TCRs) optimized for reactivity to specific peptides and decreased cross-reactivity to non-target peptides. Advantageously, TCRs of the invention can be optimized to target cancer antigens and peptides while having reducing reactivity to healthy cells. Methods of the invention utilize a novel combination of culturing conditions that increase T-cell activation and allow for validation of TCR activity. Culturing conditions of the invention further reduce culturing times generally needed to achieve expanded reactive T-cells. Because of the robust nature of the activation and validation conditions of the present invention, variants of identified TCRs can also be optimized and validated for their response to peptides, including cancer peptides.

The invention relates to nucleic acid agents modulating the expression of SLAMF6 isoforms, compositions comprising same and methods for their use in immunomodulation. Specifically, provided are splice-switching oligonucleotides and constructs useful in cancer immunotherapy.

The present invention provides isolated T cell receptors (TCRs) that specifically bind to an HLA-displayed cancer testis antigen Melanoma-Associated Antigen A4 (MAGE-A4) peptide, as well as therapeutic and diagnostic methods of using those isolated TCRs. The present invention provides T cell receptors (TCRs) that were generated against a MAGE-A4 peptide antigen in the context of MHC (HLA-A2). The unique TCR sequences identified have shown specific binding to the small peptide MAGE-A4 presented in the groove of an HLA molecule and exhibited activation of T cells in a reporter assay.

This disclosure provides methods for producing multi-TCR T cells with enhanced anti-tumor phenotypes. The T cells are made from hematopoietic stem cells by introducing into the hematopoietic stem cells a first TCR and subsequently a second TCR.

Disclosed herein are methods for treatment of a mesothelin (MSLN)-expressing cancer in a human subject comprising administration of, e.g., a plurality of anti-MSLN T cell receptor fusion protein (TFP)-expressing T cells. A ratio of CD4+ to CD8+ T cells in a sample from the human subject may have been determined before the administration of the plurality of anti-MSLN TFP-expressing T cells. The plurality of anti-MSLN TFP-expressing T cells may comprise a pre-determined ratio of CD4+ to CD8+ T cells.

A method of treating a metastatic lesion that presents a peptide containing SLLQHLIGL (SEQ ID NO: 310) on a cell surface, including selecting a patient having a metastatic lesion and administering to the patient a composition containing recombinant T lymphocytes or activated T lymphocytes that express a T cell receptor, or a functional fragment thereof, that is reactive with, or binds to, an MHC ligand containing SLLQHLIGL (SEQ ID NO: 310).

The present invention discloses T-cell receptor of HLA-A11-restricted hepatitis B virus HBc 141-151 epitope peptide and applications thereof. The T cell receptor comprises an α chain and β chain; the α chain comprises three complementarity determining regions with amino acid sequences shown in positions 48 to 53, positions 71 to 77 and positions 112 to 121 of SEQ ID NO. 2, respectively; the β chain comprises three complementarity determining regions with amino acid sequences shown in positions 46 to 50, positions 68 to 73 and positions 111 to 122 of SEQ ID NO. 4, respectively. Experiments demonstrated that the T cell receptor exhibits both HBV polypeptide epitope-dependent activation and proliferation ability and also exhibits an ability to kill target cells both in vivo and in vitro.

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with aspartic acid. The TCRs may recognize G12D RAS presented by an HLA-DR heterodimer. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.

The present invention relates to compositions and methods for the treatment of lupus, particularly systemic lupus erythematosus. The present invention involves, amongst other things, a binding protein comprising a T cell receptor (TCR) α-chain variable (Vα or Valpha) domain and a TCR β-chain variable (Vβ or Vbeta) domain, wherein the binding protein is capable of binding to a complex of a fragment of a Smith protein and an HLA-DR15 or HLA-DR3 molecule.