The disclosure relates to methods of culturing and expanding CD4+ and/or CD8+ T cells in culture. In some embodiments, the methods include expanding, proliferating and storing lymphocytes in tissue culture by exposing the lymphocytes to a combination of cytokines and/or nucleic acids expressing cytokines or functional fragments or variants thereof. The disclosure further relates to methods of generating and manufacturing CD4+ and/or CD8+ T cells that are specific to one or a plurality of viral antigens.

The invention is concerned with a fusion protein comprising interleukin 13 and a regulatory cytokine, for example, an interleukin chosen from interleukin 4, interleukin 10, interleukin 27, interleukin 33, transforming growth factor beta 1, transforming growth factor beta 2, and interleukin 13, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of a condition characterized by pathological pain, chronic pain, neuro-inflammation and/or or neurodegeneration.

The invention relates to an interleukin-21 protein (IL21) mutant and application thereof. The mutant is with ILE at position 16 and SER at position 70 of the amino acid sequence of the wild-type IL21 both mutating into CYS, and a disulfide bond forming between the two mutated CYSs. The amino acid sequence of the wild-type IL21 is shown in SEQ ID NO.1. The invention also relates to a fusion protein containing the IL21 mutant protein and a use of the IL21 mutant protein or the fusion protein in the preparation of a medicine and, preferably, the medicine regulates or activates immunity or are an anti-tumor medicine. The invention also relates to the use of the IL21 mutant, the IL21/4 mutant or the fusion protein in the preparation of a formulation for promoting the differentiation and proliferation of B cell, the differentiation and proliferation of T cell, the differentiation and proliferation of NK cell.

Conditionally active receptor agonists that, when activated, bind to IL-2 receptor β.sub.c heterodimer (IL-2Rβ.sub.c), IL-4 receptor α.sub.c heterodimer (IL-4Rα.sub.c), or IL-13 receptor a subunit (IL˜13 Rα) are disclosed, as are components of the conditionally active receptor agonists and methods for using the conditionally active receptor agonists.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL4R and/or IL4, and methods of use thereof.

The present invention provides methods for inducing an immune response to a pathogen in neonatal mammals. In particular, the present invention provides methods for inducing an immune response to a pathogen in a neonatal mammal comprising administering to the neonatal mammal a composition comprising a fusion protein between interleukin-4 (IL-4) and a first antigen of the pathogen.

Recombinant oncolytic viruses (OVs) that express one or more metabolic modulator proteins, such as an adipokine (e.g., leptin or chemerin), insulin, and/or IGF-1, and methods of their use to treat cancer, for example in immunotherapy anti-cancer treatments. In some examples, such recombinant OVs and methods increase T cell infiltration into the tumor or tumor microenvironment.

De novo designed polypeptides that bind to IL-2 receptor β.sub.c heterodimer (IL-2Rβ.sub.c), IL-4 receptor α.sub.c heterodimer (IL-4Rα.sub.c), or IL-13 receptor α subunit (IL-13Rα) are disclosed, as are methods for using and designing the polypeptides.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.