A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y177 mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y177 mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.

There is described herein a method for inducing Tc22 lineage T cells from a population of CD8+ T cells, the method comprising: a) providing a population of CD8+ T cells; b) activating the population of CD8+ T cells; and c) culturing or contacting the population of CD8+ T cells with IL-6.

There is described herein a method for inducing Tc22 lineage T cells from a population of CD8+ T cells, the method comprising: a) providing a population of CD8+ T cells; b) activating the population of CD8+ T cells; and c) culturing or contacting the population of CD8+ T cells with IL-6.

The present application relates to conjugates comprising interleukin 2 (IL2), and a mutant of tumour necrosis factor, such as tumour necrosis factor alpha (TNFα), and an antibody molecule. The antibody molecule preferably binds to an antigen associated with neoplastic growth and/or angiogenesis, such as the Extra-Domain A (EDA) or Extra-Domain B (EDB) of fibronectin. The conjugate may be used in the treatment of cancer.

A cancer vaccine is provided including a recombinant nucleic acid encoding a self-activating chimeric signaling protein, and especially chimeric TNF family ligand-receptor proteins, and a tumor-associated antigen. In a preferred embodiment, the cancer vaccine may further include a nucleic acid segment encoding an IL-15 superagonist. In addition, the cancer vaccine can be co-administered with a genetically modified bacteria or yeast as an adjuvant to increase the payload expression of the cancer vaccine. Advantageously, cells expressing such combination of molecules will enhance immune reaction against tumor cells. Compositions and methods are presented that allow for an enhanced immune response against a vaccine composition, and particularly a recombinant adenoviral expression system that is used as a therapeutic agent. Most preferably, immune therapeutics are administered such that a protein or nucleotide are co-located with a therapeutic antigen, preferably via co-expression of the protein.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.

The present invention relates to methods, compositions, and kits for increasing the activation of effector T cells in a subject or inhibiting the activation of effector T cells in a subject by increasing or decreasing TNFR2 (CD 120b) signaling respectively. The present invention also relates to methods, compositions, and kits for treating diseases such as cancer, infections, and autoimmune diseases.

The present disclosure is directed to a method of treating neurological disorder comprising peripheral administration to a patient in need thereof a DN-TNF polypeptide that inhibits the activity of soluble TNF- but not transmembrane TNF-α.