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.

Systems and methods of coding for and isolating a fusion protein are provided. The fusion protein may be expressed by a DNA sequence and comprise an adenylate kinase linked by its carboxy-terminus to a biologically active polypeptide or protein. Later processing steps include isolating the biologically active polypeptide or protein via affinity elution of the fusion proteins with substrate analog of adenylate kinase.

Systems and methods of coding for and isolating a fusion protein are provided. The fusion protein may be expressed by a DNA sequence and comprise an adenylate kinase linked by its carboxy-terminus to a biologically active polypeptide or protein. Later processing steps include isolating the biologically active polypeptide or protein via affinity elution of the fusion proteins with substrate analog of adenylate kinase.

The invention relates to novel TNF family ligand trimer-containing antigen binding molecules comprising (a) at least one moiety capable of specific binding to a target cell antigen, (b) a polypeptide comprising three ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by peptide linkers and (c) a Fc domain composed of a first and a second subunit capable of stable association, and to methods of producing these molecules and to methods of using the same.

The invention relates to novel TNF family ligand trimer-containing antigen binding molecules comprising (a) at least one moiety capable of specific binding to a target cell antigen, (b) a polypeptide comprising three ectodomains of a TNF ligand family member or fragments thereof that are connected to each other by peptide linkers and (c) a Fc domain composed of a first and a second subunit capable of stable association, and to methods of producing these molecules and to methods of using the same.

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.

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.

Heterodimers are provided. Accordingly, there is provided a heterodimer comprising a dimerizing moiety attached to at least one amino acid sequence of at least one type I membrane protein capable of at least binding a natural ligand or receptor of said at least one type I membrane protein and to at least one amino acid sequence of at least one type II membrane protein capable of at least binding a natural ligand or receptor of said at least one type II membrane protein. Also provided are nucleic acid constructs and systems encoding the heterodimer, host-cells expressing same and methods of use thereof.

The present system and method are useful for the removal of immune inhibitors such as soluble TNF receptors from the body fluid of cancer patients. In some embodiments, soluble TNF-Receptors 1 and 2 are selectively removed from plasma at 80% or more efficiency. In some embodiments, the system includes an immobilized capture ligand of a single chain TNFα. The system and method are useful for the treatment of different cancer types, stages and severity.

The present system and method are useful for the removal of immune inhibitors such as soluble TNF receptors from the body fluid of cancer patients. In some embodiments, soluble TNF-Receptors 1 and 2 are selectively removed from plasma at 80% or more efficiency. In some embodiments, the system includes an immobilized capture ligand of a single chain TNFα. The system and method are useful for the treatment of different cancer types, stages and severity.