The invention provides compositions and methods for generating improved T cells having increased Ezh2 activity and methods of use thereof in the treatment of cancer and chronic infection.

Disclosed are compositions, kits, and methods for identifying genes that are involved in T-cell trafficking. In particular, the compositions, kits, and methods may be used to identify genes involved in T-cell trafficking and/or infiltration into tumors such as genes that encode immune checkpoint regulators and/or stimulatory agents. The disclosed compositions, kits, and methods utilize the Sleeping Beauty transposon system in a mouse tumor model to identify genes that are involved in T-cell trafficking and infiltration into tumors. The genes identified in the disclosed methods may provide immunotherapy targets in the tumor microenvironment. The identified genes may be utilized in order to develop therapies that enhance T-cell trafficking and infiltration into tumors and/or T-cell killing of tumors such as in chimeric antigen receptor (CAR) T cell therapies.

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.

Disclosed are: a virus vector in which a gene encoding an antigenic polypeptide is integrated in human parainfluenza virus type 2 gene, wherein the antigenic polypeptide is expressed in the form of a fusion protein with a viral structural protein; and a method for producing the same. The virus vector of the present invention contains a quantitatively large amount of the antigenic peptide on the virus particle and can efficiently deliver the antigenic polypeptide to a target cell.

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.

Methods and compositions for treating cancers (e.g., neural cancers) by dendritic cell vaccination are provided herein.

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 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.

Disclosed are methods of treating or preventing cancer in a mammal, the method comprising: (a) isolating T cells from a tumor sample from the mammal, wherein the isolated T cells are one or both of exhausted and differentiated, and the isolated T cells have antigenic specificity for a tumor-specific antigen expressed by the tumor sample from the mammal, wherein the tumor-specific antigen is a tumor-specific neoantigen or an antigen with a tumor-specific driver mutation; and optionally expanding the numbers of isolated, tumor antigen-specific T cells; and (b) administering to the mammal (i) the isolated T cells of (a) and (ii) a vaccine which specifically stimulates an immune response against the tumor-specific antigen for which the isolated T cells have antigenic specificity.

Disclosed are methods of treating or preventing cancer in a mammal, the method comprising: (a) isolating T cells from a tumor sample from the mammal, wherein the isolated T cells are one or both of exhausted and differentiated, and the isolated T cells have antigenic specificity for a tumor-specific antigen expressed by the tumor sample from the mammal, wherein the tumor-specific antigen is a tumor-specific neoantigen or an antigen with a tumor-specific driver mutation; and optionally expanding the numbers of isolated, tumor antigen-specific T cells; and (b) administering to the mammal (i) the isolated T cells of (a) and (ii) a vaccine which specifically stimulates an immune response against the tumor-specific antigen for which the isolated T cells have antigenic specificity.