The invention provides methods for the ex-vivo expansion of CD4+CD25+ Tregs. The invention provides a method for producing ex vivo expanded Tregs that may be used to inhibit unwanted human immune responses against self-antigens or allergens. Additionally, the ex vivo expanded Tregs may provide treatment for inflammatory/autoimmune diseases.

Provided are methods and systems for determining functional relationships between ex vivo skin models and an inflammatory skin condition. Also provided are methods and systems for identifying modulators of inflammation of skin, as well as the use of modulators identified by such methods or systems for the preparation of cosmetic compositions, personal care products, or both.

A method of producing an engineered T cell population includes obtaining a cell population comprising a CD8+ T cell, isolating the CD8+ T cell from the obtained cell population, activating the isolated CD8+ T cell, introducing a nucleic acid encoding a T cell receptor (TCR) binding to an antigen in a complex with an MHC molecule into the activated CD8+ T cell, and expanding the introduced CD8+ T cell to obtain the engineered T cell population.

The invention provides methods for the ex-vivo expansion of CD4+CD25+ Tregs. The invention provides a method for producing ex vivo expanded Tregs that may be used to inhibit unwanted human immune responses against self-antigens or allergens. Additionally, the ex vivo expanded Tregs may provide treatment for inflammatory/autoimmune diseases.

In some embodiments, compositions and methods relating to isolated artificial antigen presenting cells (aAPCs) are disclosed, including aAPCs comprising a myeloid cell transduced with one or more viral vectors, such as a MOLM-14 or a EM-3 myeloid cell, wherein the myeloid cell endogenously expresses HLA-AB/C, ICOS-L, and CD58, and wherein the one or more viral vectors comprise a nucleic acid encoding CD86 and a nucleic acid encoding 4-1BBL and/or OX40L and transduce the myeloid cell to express CD86 and 4-1BBL and/or OX40L proteins. In some embodiments, methods of expanding tumor infiltrating lymphocytes (TILs) with aAPCs and methods of treating cancers using TILs after expansion with aAPCs are also disclosed.

The invention features methods of producing compositions enriched in Tregs and methods for treating immunological disorders using these compositions. The invention also features methods for producing compositions enriched in lymphocytes and depleted of Tregs and the use of these compositions in the treatment of proliferative disorders.

A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.

The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Several embodiments disclosed herein relate to methods and processes for the co-expansion of multiple types of immune cells, in order to generate a mixed cell population. Some embodiments relate to the use of various stimuli specific to the various subpopulations to achieve expansion of those subpopulations at a particular time in a culturing process in order to generate an expanded population of immune cells having a desired ratio of the various subpopulations. In several embodiments, such mixed cell populations exhibit desirable characteristics, such as cytotoxic effects against tumor cells that enhance the efficacy of cancer immunotherapy.

The present invention relates to a cell therapy composition for preventing or treating immune disease comprising mesenchymal stem cells and immunoregulatory T-cells as an active ingredient. By infusing mesenchymal stem cells and immunoregulatory T-cells, which are the cellular therapeutic agent of the present invention, into bone marrow transplant animals, rejection to the host is suppressed after the engraftment of the transplanted bone-marrow to thus obtain the effect of reducing graft-versus-host disease and immune disease. Moreover, the effect of such GVHD reduction is much greater than the one obtained when only mesenchymal stem cells are infused. Accordingly, the cell therapy composition of the present invention having the above-mentioned effects can be useful in the prevention or treatment of immune disease.