Disclosed are cysteine variants of interleukin-11 (IL-11) and methods of making and using such proteins in therapeutic applications.

The invention provides methods for treating fibrosis and/or cancer in a subject in need thereof. The methods include providing a composition comprising an inhibitor of IL-4/IL-13 receptor function and administering an effective amount of the composition to the subject to treat fibrosis and/or cancer.

The present disclosure relates to targeted degradation platform technology. For example, the present disclosure relates to bispecific binding agents for degrading endogenous proteins, whether membrane-associated or soluble, using the lysosome pathway. The disclosure also provides methods useful for producing such agents, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various disorders.

A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13R?2 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.

Variant IL-13 polypeptides are provided, which are engineered to have one or more of the following properties: (a) altered affinity for IL-13R?2, relative to the native human IL-13 protein; (b) altered affinity for IL-13R?1 relative to the native human IL-13 protein; (c) a disruption in the binding site for IL-4R? relative to the native human IL-13 protein.

The present invention relates to interleukin-4 receptor binding fusion proteins. More specifically, the invention provides, in part, fusion proteins that include an interleukin-4 receptor binding protein moiety joined to a pro-apoptotic Bcl-2 family member protein moiety.

The present invention relates to interleukin-4 receptor-binding fusion proteins. More specifically, the invention provides, in part, fusion proteins that include an interleukin-4 or interleukin-13 protein moiety joined to an anti-apoptotic Bcl-2 family member protein moiety.

The invention provides methods for treating fibrosis and/or cancer in a subject in need thereof. The methods include providing a composition comprising an inhibitor of IL-4/IL-13 receptor function and administering an effective amount of the composition to the subject to treat fibrosis and/or cancer.

A compound comprising, in combination: a cell surface binding ligand or internalizing factor, such as an IL-13R?2 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 disclosure relates to immunotoxins, particularly immunotoxins useful for treating IL-13R?2 expressing cancer, or reducing perineural invasion by an IL-13R?2 expressing cancer. Immunotoxins that specifically bind IL-13R?2, nucleic acids encoding the immunotoxins, vectors including the nucleic acids encoding the immunotoxins, and host cells expressing the immunotoxins are provided. Also provided are pharmaceutical compositions including the immunotoxin and methods of treating a subject with cancer, including administering to the subject the immunotoxin alone or in combination with other cancer therapies. Also provided are methods of reducing perineural invasion (PNI) and reducing pain associated with PNI, by administering a therapeutically effective amount of the immunotoxin or IL-13-PE immunotoxin.