The present invention relates to improved methods in the separation recombinant polypeptides with post-translational modifications from complex mixtures through the use of a cation exchange medium.

The present invention relates, inter alia, to compositions and methods, including chimeric proteins having a first domain comprising an extracellular domain of a first transmembrane protein, a first secreted protein, or a first membrane-anchored extracellular protein and a second domain comprising an extracellular domain of a second transmembrane protein, a second secreted protein, or a second membrane-anchored extracellular protein, in which either or both of the first domain and the second domain decreases self-directed immune system activity when bound to its ligand/receptor. Accordingly, the present invention find use in the treatment of autoimmune diseases.

A chimeric fusion polypeptide is provided comprising an extracellular domain of a canine TNF receptor p60 or p80 polypeptide conjoined to an Fc region of a canine IgG immunoglobulin heavy chain. The chimeric fusion polypeptide may be used in the treatment or prevention of conditions in canines mediated by TNF expression.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Compositions specific for TNF-receptor superfamily member 25 (TNFRSF25, DR3) modulate the immune response by regulating T regulatory cells.

The present invention relates to an inhibitor of necroptosis for use in preventing the metastasis of tumours. Further, the present invention relates to a method of preventing the metastasis of tumours by inhibiting necroptosis and to a method for modulating the transmigration of metastasising tumour cells through endothelium by modulating necroptosis as well as to an in-vitro method of identifying an inhibitor of necroptosis suitable as a lead compound and/or as a medicament for the prevention of tumour metastasis. Moreover, the present invention also relates to a method of identifying necroptotic and necrotic cells.

It was found that TRAIL-induced death signaling was largely diminished by lysosomal degradation system. Inhibition of lysosomal degradation by small molecules led to accumulation of DR5 in lysosomes and reversed TRAIL resistance in almost all cancer cells. Redirecting TRAIL-induced signaling away from lysosomal degradation may therefore induce massive cell death and overcome TRAIL resistance. Taking advantage of bioactive protein transduction domains (PTD) and signaling peptides, such as TAT peptide from HIV TAT protein, NLS (nuclear localization signal), MTS (mitochondrial targeting sequence), a series of new TRAILs fused with these peptides was constructed. It was found that TRAIL fused with bioactive peptide exerted remarkably high potency in inducing cell death in cancer cells, but not normal cells.

It is disclosed herein that osteoprotegerin increases human beta cell proliferation and survival. Methods are provided for increasing beta cell proliferation, but contacting a beta cell with an effective amount of osteoprotegerin, a functional fragment, variant or fusion protein thereof. Methods are also provided for treating a human subject with diabetes, comprising administering to the subject a therapeutically effective amount of osteoprotegerin, functional variant or fusion protein thereof.

Polypeptides and agents that bind a TNF receptor superfamily protein are disclosed, particularly agents that specifically bind GITR, OX40, or CD40. The polypeptides or agents may include fusion polypeptides, particularly polypeptides comprising GITRL, OX40L, or CD40L and/or bispecific agents. Also disclosed are methods of using the polypeptides or agents for inducing and/or enhancing the immune response, as well as methods for the treatment of diseases such as cancer.

The present disclosure provides various core constructs. According to embodiments of the present disclosure, the core construct can be used to configure pharmaceutical molecules. In particular, the core construct may be conjugated with a functional element via the click chemistry.