Provided by the disclosure are compositions and methods for modulating differentiation of regulatory T cells. In some embodiments, methods include selectively decreasing IL-23R activity and/or IL-23R expression without significantly decreasing IL-12R activity and/or IL-12R expression.

Embodiments of the disclosure include methods and compositions for producing T cell receptor (TCR) polypeptides specific for hematological neoantigens. In specific embodiments. T cells directed to one or more hematological neoantigens are produced following exposure of PBMCs to peptides that encompass one or more neoantigens, and the TCRs in the produced T cells are tested for efficacy and identified. The neoantigen-specific TCRs are utilized in a variety of immunotherapies.

Disclosed is a method of producing non-exhausted immature dendritic cells (DCs) originating front at two different, allogeneic donors. In the method, a mixture of allogeneic leukocytes, which allogeneic leukocytes have been obtained from at least two different, allogeneie donors is provided. Subsequently, allogeneic monocytes are isolated from the mixture of allogeneic leukocytes. Thereafter, non-exhausted immature DCs are generated from said isolated allogeneic monocytes.

The present invention relates to an in vitro method for priming genetically modified T cells suitable for administration to a patient having a tumor. The invention is also directed to the composition obtained by the method and uses thereof.

A method of producing a population of CD8+ Tc9 lymphocytes is provided including priming a population of nave CD8+ T cells by contacting the population of nave CD8+ T cells with an immunogenic peptide, in the presence of a Tc9 supportive environment, thereby producing a population of CD8+ Tc9 lymphocytes which secrete IL-9. Purified populations of CD8+Tc9 cells are also disclosed herein, as are method for their use in the treatment of cancer in a subject.

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

Disclosed is a method of producing non-exhausted immature dendritic cells (DCs) originating from at two different, allogeneic donors. In the method, a mixture of allogeneic leukocytes, which allogeneic leukocytes have been obtained from at least two different, allogeneic donors is provided. Subsequently, allogeneic monocytes are isolated from the mixture of allogeneic leukocytes. Thereafter, non-exhausted immature DCs are generated from said isolated allogeneic monocytes.

The present invention relates to methods for stimulating antigen-specific T cell responses. In particular, the invention relates to a method for stimulating antigen (Ag)-specific T cell responses in a blood sample or PBMC sample isolated from a subject comprising the step consisting in culturing said blood or PBMC sample in a appropriate culture medium which comprises an amount of IL-1beta and an amount of a least one antigen.

The invention relates to a method for producing tolerogenic dendritic cells (tolDCs) with specific antigens, comprising the steps of: (a) culturing precursors of dendritic cells in an animal-serum-free medium, using cytokines, IL-4 and GM-CSF, in order to differentiate same in dendritic cells; (b) producing apoptotic cells; (c) culturing the dendritic cells obtained in step (b) in the presence of compounds having anti-inflammatory activity; (d) co-culturing the dendritic cells from step (d) with the apoptotic cells from step (c), such as to stimulate the endocytosis of the apoptotic cells by the dendritic cells; (e) and, by means of identification based on phenotypic evaluation, determining the production of tolerogenic dendritic cells (tolDCs) with specific antigens. The invention also relates to the tolDC cells produced with said method and to the use of said tolDCs with specific antigens in the production of a drug suitable for the treatment of systemic lupus erythematosus.

A method of producing a population of CD8+ Tc9 lymphocytes is provided including priming a population of nave CD8+ T cells by contacting the population of nave CD8+ T cells with an immunogenic peptide, in the presence of a Tc9 supportive environment, thereby producing a population of CD8+ Tc9 lymphocytes which secrete IL-9. Purified populations of CD8+ Tc9 cells are also disclosed herein, as are method for their use in the treatment of cancer in a subject.