Provided herein are methods and compositions for treating a subject having cancer by administering to the subject a cancer vaccine accompanied by administration of a long acting IL-2R??-biased agonist.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided.

Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.

Disclosed are methods of preparing an isolated population of dendritic cells, isolated populations of dendritic cells prepared by the methods, and pharmaceutical compositions comprising the isolated population of dendritic cells. Also disclosed are methods of treating or preventing cancer using the isolated population of dendritic cells or pharmaceutical compositions.

Provided is directed to the field of immunotherapy. Specifically, provided are compositions and methods for improved T cell modulation ex vivo and in vivo and for the treatment of cancer and other pathologies. More specifically, embodiments of the subject matter are directed to the use of soluble NTB-A polypeptides or agonists thereof for the treatment of cancer patients, for preventing and treating cytopenia in susceptible patients, and for the ex vivo preparation of improved cell compositions.

The present invention relates to retroviral particle comprising a protein derived from the Gag polyprotein, an envelope protein, optionally an integrase and at least two encapsidated non-viral RNAs, the encapsidated non-viral RNAs each comprising an RNA sequence of interest bound to an encapsidation sequence, each encapsidation sequence being recognized by a binding domain introduced into the protein derived from the Gag polyprotein and/or into the integrase, and at least one of said sequences of interest of the encapsidated non-viral RNAs comprises a part coding at least one epitope and/or at least one molecular structure specifically recognizing an epitope.

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.

Aspects of the present disclosure relate to methods and compositions for genetic modification of immune cells to generate immune cells that do not secrete TGF-?1. Also disclosed are methods for use of such genetically modified immune cells, including immunotherapeutic methods for the treatment of cancer. Further aspects of the disclosure are directed to human CD8.sup.+ cells comprising a genetic modification that prevents the cells from secreting TGF-?1.

The present disclosure provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to immunoresponsive cells comprising antigen recognizing receptors (e.g., chimeric antigen receptors (CARs) or T cell receptors (TCRs)), and expressing increased level of IL-18. In certain embodiments, the engineered immunoresponsive cells are antigen-directed and resistant to immunosuppression and/or have enhanced immune-activating properties.