The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to an intracellular ligand which is released from a cell as a result of necrosis; and (ii) a cytokine receptor endodomain.

Contemplated treatment compositions and methods are directed to co-administration of sensitized genetically modified NK cells and recombinant IL-12, wherein the genetically modified NK cells were preferably sensitized by constitutive exposure to IL-2 and wherein the IL-12 is expressed from a recombinant virus or given as an IL-12-antibody conjugate. Such treatment increases IFN secretion by the sensitized NK cells, and advantageously also increases expression of NKG2D.

Vaccine composition containing a mutant of the human Interleukin-15 (IL-15). The use of said mutant polypeptide of human IL-15 to manufacture a medicament for the active immunotherapy of diseases associated with IL-15 overexpression, including some autoimmune diseases and hematological malignancies. Administration to an individual that needs it of a therapeutically effective amount of the vaccine, that comprises the mutant polypeptide of the human IL-15 of the invention, constitutes a method for the therapy of IL-15 over-expressing related diseases.

The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

The invention provides humanized mouse anti-human IL-31 antibodies and antibody fragments that are capable of binding IL-31 and thereby neutralizing, inhibiting, limiting, or reducing the proinflammatory or pro-pruritic effects of IL-31.

A non-injectable formulation or formulation for instillation, including self-assembling hydrogels formed of gelators such as the Food and Drug Administration's Generally Regarded as Safe (GRAS) compounds like ascorbyl palmitate, in the form of capsules, tablets, oral suspensions, enemas, and rectal or vaginal suppositories or inserts have been developed. In a preferred embodiment, the formulation contains anti-inflammatories, anti-infectives, or other therapeutic, prophylactic, or diagnostic agents that can be administered orally, especially when lower blood levels relative to tissue levels of agent are preferred. In the most preferred formulation, the composition contains tacrolimus-loaded ascorbyl palmitate gel microfibers containing nanostructures (hydrogels).

Methods are disclosed for inhibiting the development of a tumor in a subject. The methods include administering to a subject a therapeutically effective amount of a dominant negative tumor necrosis factor (DN-TNF)- protein and/or a nucleic acid encoding the DN-TNF- protein. The DN-TNF- protein and/or a nucleic acid encoding the DN-TNF- protein can be administered alone or in combination with other agents.

A bifunctional polypeptide comprising a specific binding partner for a peptide-MHC epitope, such as an antibody or T cell receptor, and an immune effector, such as an antibody or a cytokine, the immune effector part being linked to the N-terminus of the peptide-MHC binding part.

The disclosure provides interleukin 37 (IL-37) fusion proteins, methods of making IL-37 fusion proteins including constructs used to express IL-37 fusion proteins, and methods of using IL-37 fusion proteins. In some embodiments, the IL-37 fusion protein includes amino acids 46-206 of isoform B of IL-37 and a heavy chain portion of an antibody.

Compositions and methods for delivering immune modulatory molecules to result in a therapeutic effect are disclosed. The compositions and methods use stably integrating lentiviral delivery systems. The methods are useful for therapeutically and prophylactically treating cancer such as leukemia.