A composition useful for alleviating or treating pain and uses thereof are disclosed. The composition containing glutamate decarboxylase and a gene coding for an anti-inflammatory cytokine. A method for alleviating or treating pain of a subject includes administering the composition to the subject.

Provided herein are anaplastic lymphoma kinase chimeric antigen receptors (ALK CARs). The invention also provides polynucleotides encoding ALK CARs, engineered immune cells comprising an ALK CAR, pharmaceutical compositions thereof, and kits for administering the same. Methods of treating a subject with a disease by administering the ALK CAR or engineered immune cell comprising an ALK CAR, or pharmaceutical compositions thereof, are also provided.

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.

Methods for using the human interleukin-4 receptor (IL-4) as a biomarker for determining patent populations for treatment, predicting disease treatment efficacy, and predicting disease treatment prognosis in a variety of cancers, in particular glioblastoma and recurrent glioblastoma.

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 invention provides a polynucleotide including at least one of (a) a sequence encoding a fusion protein including an antigen-presenting MHC molecule capable of being presented extramembranously of an extracellular vesicle; (b) a sequence encoding a fusion protein including a T cell stimulating cytokine or a subunit thereof capable of being presented extramembranously of an extracellular vesicle; (c) a sequence encoding a fusion protein including a T cell co-stimulatory molecule capable of being presented extramembranously of an extracellular vesicle; (d) a sequence encoding a fusion protein including an antigen-presenting MHC molecule and a T cell stimulating cytokine or a subunit thereof capable of being presented extramembranously of an extracellular vesicle; and (e) a sequence encoding a fusion protein including an antigen-presenting MHC molecule, a T cell stimulating cytokine or a subunit thereof, and a T cell co-stimulatory molecule capable of being presented extramembranously of an extracellular vesicle.

Embodiments relate to peptide antagonists of γc-family cytokines, which is associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. Traditional approaches to inhibiting γc-cytokine activity involve raising neutralizing antibodies against each individual γc-cytokine family member/receptor subunit. However, success has been limited and often multiple γc-cytokine family members co-operate to cause the disease state. Combinatorial use of neutralizing antibodies raised against each factor is impractical and poses an increased risk of adverse immune reactions. The present embodiments overcome these shortcomings by utilizing peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. Such approach allows for flexibility in antagonist design. In several embodiments, peptides exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.

Devices, systems, and methods can be used for the automated production of dendritic cells (DC) from dendritic cell progenitors, such as monocytes obtained from peripheral blood. The invention makes it possible to obtain sufficient quantities of a subject's own DC for use in preparing and characterizing vaccines, for activating and characterizing the activation state of the subject's immune response, and to aid in preventing and/or treating cancer or infectious disease.

To provide extracellular vesicles capable of satisfactorily activating, etc., antigen-specific T cells. Provided are said antigen-presenting extracellular vesicles that present an antigen-presenting MHC molecule and a T-cell-stimulating cytokine extramembranously.

Provided herein are, inter alia, multi-specific ligand binding complexes capable of binding tumor-associated antigens and effector cell activating ligands. The complexes provided herein may include a first ligand binding domain (e.g., a Fab) capable of binding a tumor antigen. The complexes further include a second ligand binding domain (e.g., IL-15) non-covalently and/or covalently attached to a second ligand binding domain enhancer. The complexes provided herein are, inter alia, useful for the treatment of cancer.