The disclosure relates to compositions and kits comprising CAR-T cells and GSK3 inhibitors, including, use of such compositions and/or kits in the therapy of diseases such as cancer.

Provided herein is a construct comprising, in combination: an EphA3, EphA2 and/or EphB2 binding ligand; and at least one effector molecule. In some embodiments, the at least one effector molecule comprises a therapeutic agent, a nanoparticle, a detectable group, a lipid, or a liposome. In some embodiments, the construct is a fusion protein and/or a covalent conjugate. Further provided is a construct comprising, in combination: a ligand that binds to EphA2, EphA3 and/or EphB2; a ligand that binds to IL-13R2; and at least one effector molecule. Also provided are methods of use thereof for treating cancer.

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

Chimeric transmembrane immunoreceptors (CAR) which include an extracellular domain that includes IL-13 or a variant thereof that binds interleukin-13R2 (IL13R2), a transmembrane region, a costimulatory domain and an intracellular signaling domain are described.

Methods and compositions are provided for enhancing anti-tumor effector immune cells with a targeting construct a human IL-13 superkine. Cytokine or additional co-stimulatory sequences may also be included to enhance the tumoricidal effects of the cells.

A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13R2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

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

A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13R2 binding ligand; at least one effector molecule (e.g., one, two, three or more effector molecules); optionally but preferably, a cytosol localization element covalently coupled between said binding ligand and said at least one effector molecule; and a subcellular compartment localization signal element covalently coupled between said binding ligand and said at least one effector molecule (and preferably with said cytosol localization element between said binding ligand and said subcellular compartment localization signal element). Methods of using such compounds and formulations containing the same are also described.

The present invention relates to: a fusion polypeptide in which an anti-inflammatory polypeptide and a ferritin monomer fragment are bound; and a pharmaceutical composition for treating inflammatory diseases, containing the same as an active ingredient and, more specifically, to: a fusion polypeptide in which an anti-inflammatory polypeptide is fused to an N-terminus and/or a C-terminus of a ferritin monomer fragment from which a portion of a fourth loop and a fifth helix, of a human derived ferritin monomer, are removed; and a use thereof for treating inflammatory diseases. As in the above, the fusion polypeptide, which has an amino acid sequence represented by SEQ ID NO: 1 and in which an anti-inflammatory polypeptide is fused to an N-terminus and/or a C-terminus of a fragment of a human-derived ferritin monomer, can fuse two types of anti-inflammatory polypeptides, acting through different mechanisms, into a nano cage and administer the same, and thus the fusion polypeptide can exhibit an excellent effect in the treatment of inflammatory diseases including sepsis.