The present disclosure relates to antigen specific tolerogenic antigen presenting cells presenting antigenic portions of an autoantigen and to related compositions, methods and systems.

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.

The present invention relates to an agent for the treatment and/or prophylaxis of an autoimmune disease, an agent for the formation of regulatory T cells (T.sub.Reg) in an organism and various methods in which the agents according to the invention are used.

The invention features therapies using an IL-15-based superagonist complex to effectively treat subjects with cancer.

The present disclosure provides an isolated protein comprising at least one antibody variable region that is capable of binding to peptidase inhibitor 16 (PI16), wherein the protein is also capable of competitively inhibiting binding of an antibody produced by a hybridoma designated CRCBT-02-001 deposited with the ATCC under Accession Number PTA-10685 to PI16. The present invention also provides use of the protein, e.g., in diagnosis, therapy or to isolate cells, preferably Treg cells.

The present invention is directed to methods for increasing T-cell effector cell to regulatory T cell ratio. The invention is further directed to methods of treating, protecting against, and inducing an immune response against a tumor, comprising the step of administering to a subject a recombinant Listeria strain, comprising a fusion peptide that comprises an LLO fragment and tumor-associated antigen.

T cells harvested from an ALS patient are subjected to a de-differentiation and re-differentiation process to yield T.sub.REG/Th2 hybrid T cells and are then administered to the ALS patient as a cell therapy. The harvested T cells are first cultured in medium containing vitamin D, temsirolimus, and an IL-2 signaling inhibitor to de-differentiate the cells and then the de-differentiated cells are then transferred to a culture medium with IL-2, IL-4, and TGF-.

Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine.

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.

Genetically modified compositions, such as non-viral vectors and T cells, for treating cancer are disclosed. Also disclosed are the methods of making and using the genetically modified compositions in treating cancer.