Provided herein are monoclonal antibodies that specifically bind IL-13RA2 with cross-reactivity in humans and canines. Also provided are methods of use of the antibodies in the treatment and monitoring of cancers.

This disclosure provides a method of preventing, alleviating or treating a condition (i.e., neutropenia) in a subject in need thereof, the condition characterized by compromised white blood cell production in the subject. The method includes administering to the subject a therapeutically effective amount of a protein complex on the same day as a chemotherapy regimen, wherein the protein complex is a modified human granulocyte-colony stimulating factor (hG-CSF) covalently linked to an immunoglobulin Fc region via a non-peptidyl polymer. The non-peptidyl polymer is site-specifically linked to an N-terminus of the immunoglobulin Fc region, and the modified hG-CSF comprises substitutions in at least one of Cys17 and Pro65.

The present application relates to the treatment of pulmonary hypertension (PH) using interleukin-9 (IL9) and particularly, although not exclusively, to the treatment of PH using IL9 conjugated to a specific binding member that binds an antigen associated with tissue and/or vascular remodelling, such as the Extra Domain-A (ED-A) of fibronectin. Conjugates comprising a specific binding member that binds an antigen associated with tissue and/or vascular remodelling, such as ED-A, and IL9 that are suitable for the treatment of PH, in particular conjugates in which IL9 is conjugated to a single-chain Fv that binds ED-A or in which IL9 is conjugated an IgG that binds ED-A, are also disclosed.

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Disclosed herein are methods for treating a cancer in a subject in need thereof, comprising administering IL-2 conjugates in combination with pembrolizumab.

The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.

The present invention provides novel IL-12 Fc fusion proteins, methods of making and using the same. The IL-12 Fc fusion proteins are useful for treatment of cancer and can be used in combination with checkpoint blockade.

The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

Aspects of the invention provide methods for harnessing the potential of proteins that occur naturally (e.g., in humans) and that have serious but finite toxicity. Aspects of the invention relate to a quantitative systems-biological and structural approach to design a class Mof chimeric proteins that avoid the toxicity of protein drugs while retaining their desired activities. In particular, chimeric proteins containing a variant form of a natural protein fused to a targeting moiety may be administered to a subject to target a signal (e.g., induction of apoptosis) to particular cells without having a generalized toxic effect.

The present invention relates to a pharmaceutical composition comprising an interleukin-7 fusion protein to which an immunoglobulin Fc region has been fused for preventing or treating diseases caused by influenza virus A. The fusion protein comprising the immunoglobulin Fc region and IL-7 according to the present invention protects the body from infection due to influenza virus A and thus can treat diseases which can be caused by the virus.