Production and use of novel therapeutic cells, called T-Vehicles, in the allogeneic Adoptive Cell Therapy setting allows a wide range of therapeutic benefits to accrue with minimal or no risk of GVHD. T-Vehicles are created from donor T cells that are altered to contain therapeutic attributes that do not include their native antigen receptors and can deliver therapeutic benefits irrelevant of their native antigen specificity. T-Vehicles can possess highly restricted native antigen specificity that renders them unable to recognize antigens present on normal cells and incapable of initiating GVHD, making them ideal transport vehicles to deliver various therapeutic attributes in vivo. In essence, production and use of T-Vehicles is a paradigm shift that opens the door to therapeutic application of T cells in ways not previously contemplated, independent of whether or not there is an HLA match between the donor and the recipient.

The invention relates to a nucleic acid encoding, an artificial T cell receptor, or a fragment of an artificial T cell receptor, wherein the nucleic acid is operatively linked to a transcriptional regulatory sequence, and wherein the transcriptional regulatory sequence comprises a binding domain for a transcription factor that promotes a regulatory T lymphocyte phenotype and cells comprising such nucleic acids. The cells may further comprise a nucleic acid encoding the transcription factor and a targeting polypeptide. The cells of the invention are useful in medicine, in particular in the treatment of inflammatory conditions.

Embodiments of the disclosure provide compositions, kits, and methods for allogeneic hematopoietic cell transplantation (alloHCT) to patients. In an embodiment, a therapeutic composition for alloHCT includes at least first and second populations of isolated CD45+ cells (ICC). At least a portion of the CD45+ cells in the first population may have an antibody bound to a marker on the cell surface which is used to separate CD34+ cells from a mixture of nucleated cells (MNC) from donor or invitro produced blood. The MNC may comprise various cell types in various amounts, for example, about 70% CD34+ cells, less than about 5% CD3+ cells and less about 20% granulocytes. The ICC's in the second population include regulatory T cells which are typically at least about 50% of the population. Embodiments of the disclosure are particularly useful for treatment of hematologic cancers (e.g., leukemia, lymphoma), sickle cell anemia, GVHD, autoimmune and other diseases.

The invention features a method for treating graft versus host disease in a human, including administering to said human a therapeutically effective amount of a cell including a chimeric antigen receptor (CAR) which is specifically directed against an immune checkpoint molecule.

The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells.

The present invention provides a population of connective tissue derived cells that respond to interferon-gamma (IFN-) by expressing indolamine-2,3-dioxygenase (IDO) for use in preventing, treating or ameliorating one or more symptoms associated with disorders in which modulation of a subject's immune system is beneficial, including, but not limited to, autoimmune diseases, inflammatory disorders, and immunologically mediated diseases including rejection of transplanted organs and tissues.

Compositions and methods of selectively activating Akt3 are provided.

Described herein are engineered antigen presenting cells that can be capable of modulating a target T-cell in a T-cell antigen specific manner. In some embodiments, the engineered APCs can include a modified antigen presentation pathway. Also described herein are methods of making and using the engineered antigen presenting cells.

The subject matter disclosed herein is generally directed to tissue specific modulation of Th17 differentiation and pathogenicity by targeting tissue specific Th17 gene programs and gene targets. The tissue specific modulation may be used therapeutically to treat a disease or condition in the tissue where it arises. The subject matter disclosed herein is also directed to detecting tissue specific Th17 cells for diagnostic and therapeutic methods.

The present disclosure provides distinct therapeutic populations of cells that form a pharmaceutical composition useful in hematopoietic stem/progenitor cell transplant. For example, the present disclosure provides a therapeutic population of cells, comprising an enriched population of hematopoietic stem/progenitor cells, memory T cells, regulatory T cells, and wherein the population of cells is depleted of nave conventional -T cells. The present disclosure further provides methods of treatment using the therapeutic population of cells. In other embodiments, the present disclosure provides methods of producing a therapeutic population of cells.