The present invention is directed to chimeric antigen receptor (CAR) compositions and methods of their use in cancer and anti-viral immunotherapy. In particular, the CAR of the invention comprises a costimulatory signal (CSS) domain comprising herpes virus entry mediator protein (HVEM) or a functional fragment or variant thereof. CARs comprising such a HVEM CSS exhibit enhanced effector function.

The present invention relates, in part, to, chimeric proteins which include the extracellular domain of V-set and immunoglobulin domain-containing protein 8 (VSIG8) and their use in the treatment of diseases, such as immunotherapies for cancer and/or inflammatory diseases.

The present disclosure provides improved compositions for adoptive T cell therapies targeting CD33 for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith. The present disclosure also relates to adoptive T cell therapies targeting CD33 and another target antigen for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes chlorotoxin or a related toxin, or a variant of chlorotoxin or a related toxin, that binds to human glioma or other human tumor cells, a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

The present invention relates an in vitro method for detecting class II restricted CD4+ T cells in a sample. Herein a sample is contacted with an isolated complex of an MHC class II molecule and a peptide. This peptide comprises an MHC class II restricted T cell epitope of an antigenic protein and immediately adjacent thereof, or separated by a linker of at most 7 amino acids a sequence with a [CST]-xx-C or C-xx-[CST] motif. CD4+ T cells are detected by measuring the binding of the complex with cells in the sample, wherein the binding of the complex to a cell is indicative for the presence of CD4+ T cells in the sample. The present invention further relates to an isolated complex of an MHC Class II molecule and a peptide comprising an MHC class II restricted T cell epitope of an antigenic protein and immediately adjacent thereof, or separated by a linker of at most 7 amino acids a sequence with a [CST]-xx-C or C-xx-[CST] motif.

Provided herein are T cells expressing a chimeric antigen receptor (CAR) targeted to B cell activating factor receptor (BAFF-R). The CAR targeted to BAFF-R (BAFF-R CAR) described herein includes a domain that binds BAFF-R. Methods of making and using the BAFF-R CAR are also 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.

The present invention provides a recombinant viral vector, an immunogenic composition containing the same, and the use thereof. The recombinant viral vector comprises a polynucleotide encoding a fusion peptide of CD4 helper T cell epitopes, the epitope fusion peptide comprising a cytomegalovirus epitope and/or an influenza virus epitope. The epitope fusion peptide and the recombinant viral vector provided by the present invention can improve the level of cellular immune response to a target immunogen, particularly to a weak immunogen, and overcome the immune tolerance of immune system to an antigen, particularly to a tumor antigen or an infection-related antigen. The products of the present invention are suitable for enhancing the efficacy of vaccines.

Disclosed are methods of identifying immunosuppressive T.sub.R1 regulatory T cells, including methods of diagnosing the presence of immune tolerance, methods of producing immunosuppressive regulatory T cells, and methods of eliciting immune tolerance in a subject. These methods include screening T cells to detect Eomes.sup.+IL-10.sup.+ T cells or expressing recombinant Eomes in T cell populations to generate immunosuppressive regulatory T cells.

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.