Cells, such a T-cells, are provided that comprise cytokine receptors having increased activity in response to their ligand. For example, cell can comprise IL-2 and/or IL-15 receptors having increased surface expression or signaling activity. Cells of the embodiments have a significant growth advantage in the presence of cytokines and can be used, e.g., for enhanced adoptive cell transfer therapies.

The present invention describes a method for treating cancer comprising adoptive transfer of tumor antigen specific CD8+ T cells and an oncolytic virus vaccine targeting the same antigen.

Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.

The present disclosure provides methods for expanding tumor-infiltrating lymphocytes (TILs), such as tumor-infiltrating T cells, utilizing an agonist of PGC1? in vivo, ex vivo, or both. Exhausted T cells present in the TIL population fail to effectively proliferate, produce cytokines, or kill target cells. The present disclosure provides methods to correct these defects through the use of pharmacologic agents to reprogram the metabolism of the exhausted intratumoral T cells. Exemplary agonists of PGC1? include proliferator-activated receptor (PPAR)-gamma agonists (e.g., a thiazolidinedione (TZD), aleglitazar, farglitazar, muraglitazar, or tesaglitazar), AMPK activators (e.g., 5-aminoimidazole-4-carboxamide ribonucleotide, AICAR), and sirtuin activators (e.g., resveratrol, SRT1720, SRT2104, SRT2183, SRT1460). Also provided are kits can compositions that can be used with such methods.

Disclosed are T-cell receptors (TCRs) binding to tumor-associated antigens (TAAs) for targeting cancer cells, T-cells expressing same, methods for producing same, and methods for treating cancers using same. Disclosed are TCRs and their variants that bind to HLA class I or II molecules with a peptide, such as MAG-003 have the amino acid sequence of KVLEHVVRV (SEQ ID NO:1). The description further relates to peptides, proteins, nucleic acids, cells for use in immunotherapeutic methods, the immunotherapy of cancer, and 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 novel uses and methods for T cell based immunotherapies. Specifically, the invention relates to novel ligands, targets and nucleic acids and vectors encoding said targets that are useful for modulating T cell responses.

Described herein are compositions and methods for treating a disease, particularly a cancer, with an immune checkpoint modulatory agent and a strain of an Arbovirus or a strain of an Alphavirus. Also provided herein are also methods for combination therapy comprising administration of an immune checkpoint modulatory agent, tumor antigen primed dendritic cells and an Alphavirus or an Arbovirus.

The present disclosure relates to erythroid cells that have been engineered to include, e.g., at the surface of the cell, one or more exogenous stimulatory polypeptides, wherein the exogenous stimulatory polypeptides presented are sufficient to stimulate an immune killer cell. The engineered enucleated cells of the present disclosure are useful in methods of activating NK cells and/or CD8+T-cells in a subject in need thereof, such as subjects having cancer or an infectious disease, and in particular cancers or infectious diseases characterized by downregulation of MHC Class I presentation.

The present disclosure relates to artificial antigen presenting cells (aAPCs), in particular engineered erythroid cells and enucleated cells (e.g. enucleated erythroid cells and platelets), that are engineered to activate or suppress T cells.

Methods of sorting T lymphocytes in a microfluidic device are provided. The methods can include flowing a fluid sample comprising T lymphocytes through a region of a microfluidic device that contains an array of posts. The array of posts can be configured to have a critical size (D.sub.c) that separates activated T lymphocytes from na?ve T lymphocytes. Also provided are microfluidic devices having an array of posts configured to separate activated T lymphocytes from na?ve T lymphocytes, compositions enriched for T lymphocytes, particularly activated T lymphocytes that are known to be reactive to an antigen of interest, and methods of treating subjects suffering from a pathogenic disorder or cancer by administering such compositions.