A method for producing CD4/CD8 double-positive T cells, comprising the steps of: (1) culturing pluripotent stem cells in a medium to induce hematopoietic progenitor cells; and (2) culturing the hematopoietic progenitor cells obtained in the step (1) in a medium containing a p38 inhibitor and/or SDF-1 to induce CD4/CD8 double-positive T cells.

A method for producing CD4/CD8 double-positive T cells, comprising the steps of: (1) culturing pluripotent stem cells in a medium to induce hematopoietic progenitor cells; and (2) culturing the hematopoietic progenitor cells obtained in the step (1) in a medium containing a p38 inhibitor and/or SDF-1 to induce CD4/CD8 double-positive T cells.

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 nucleic acid expression cassettes that are engineered to enhance gene expression. Vectors and methods employing the expression cassettes containing novel chimeric regulatory elements are provided. The invention is particularly useful for delivery of transgenes to target cells and confers desirable properties for liver-directed and muscle-directed or liver-directed and bone-directed gene therapy. Moreover, the invention relates to a novel method of engineering tandem enhancer/promoter elements and expressing transgenes for example within liver and/or muscle cells, and delivery of therapeutics for treating various disorders.

Provided herein are combinations of an IL-2 molecule or mutein and a TNFR agonist, and complexes comprising IL-2/TNFR agonist molecules, such as Fc-bound IL-2/TNFR agonist molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

Provided herein are combinations of an IL-2 molecule or mutein and a TNFR agonist, and complexes comprising IL-2/TNFR agonist molecules, such as Fc-bound IL-2/TNFR agonist molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

The present invention provides antibodies to canine IL-4 receptor alpha that have a high binding affinity for canine IL-4 receptor alpha, and that can block the binding of canine IL-4 and/or IL-13 to canine IL-4 receptor alpha. The present invention further relates to epitopes of IL-4 receptor alpha that bind to the antibodies to canine IL-4 receptor alpha. The present invention further provides the use of the antibodies for the treatment of atopic dermatitis in dogs.

The present invention provides antibodies to canine IL-4 receptor alpha that have a high binding affinity for canine IL-4 receptor alpha, and that can block the binding of canine IL-4 and/or IL-13 to canine IL-4 receptor alpha. The present invention further relates to epitopes of IL-4 receptor alpha that bind to the antibodies to canine IL-4 receptor alpha. The present invention further provides the use of the antibodies for the treatment of atopic dermatitis in dogs.

Provided herein are target HLA-PEPTIDE antigens, e.g., HLA-PEPTIDE neoantigens and shared tumor HLA-PEPTIDE antigens, and antigen binding proteins (ABPs) that bind the target HLA-PEPTIDE antigens. Also disclosed are methods for identifying target HLA-PEPTIDE antigens as well as identifying one or more antigen binding proteins that bind a given HLA-PEPTIDE target antigen.