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.

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

A pharmaceutical composition is described, which comprises proteins and an immune checkpoint inhibitor, wherein the proteins comprise a fusion protein, and the fusion protein comprises cytokines IL12, IL2, and GMCSF. A reagent kit is also described, which comprises the pharmaceutical composition. The pharmaceutical composition or the reagent kit may be used in preparing a medicament for treating a tumor.

The present invention relates to immunoconjugates, compositions, methods and uses for treating brain tumors, especially glioma, by administration of a tumour necrosis factor alpha (TNFα) immunoconjugate.

Antibodies and meditopes that bind to the antibodies are provided, as well as complexes, compositions and combinations containing the meditopes and antibodies, and methods of producing, using, testing, and screening the same, including therapeutic and diagnostic methods and uses.

The present disclosure provides isolated polypeptide comprising an antigen binding unit directed to a cellular targete bound by an exogenous molecule. The polypeptides, cells comprising the same are useful for targeting intracellular targets or intracellular portions of a target. The compositions and methods disclosed herein have a range of utilities as therapeutics, diagnostics, research tools.

The present invention is directed to compositions including the cytokines IL-18 and IL-22 or biologically active fragments or variants thereof. In some embodiments, the compositions further include a pharmaceutically acceptable carrier. The compositions can farther include other interleukins such as IL-1β, and IL-1β can be used as a combination therapy with either IL-18 or IL-22 or biologically active fragments or variants thereof.

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.

Provided are activatable proprotein heterodimers comprising at least two separate polypeptide chains, one chain comprising an IL-2 protein fused to an IL-15 binding protein such as IL-15Rα, and another chain comprising an IL-15 protein fused to an IL-2 binding protein such as IL-2Rα, among other features including binding moieties and cleavable linkers, and related pharmaceutical compositions and methods of use thereof.

Disclosed are compositions comprising an IL-2:anti-IL-2 antibody (Ab) complex (IL-2C) and methods of using said N compositions for the treatment of microbial infections, autoimmune diseases, autoinflammatory diseases, or cancers as well the treatment of inflammatory conditions or reduction in inflammation caused by said microbial infections, autoimmune diseases, autoinflammatory diseases, or cancers.