The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

The invention features homo-multimers, e.g., homo-trimers, of TNFSF or TNF-like ligand muteins in which each TNFSF ligand or TNF-like ligand mutein monomer contains at least one cysteine residue substitution or insertion that promotes the formation of a disulfide bond with a cysteine residue on a neighboring TNFSF or TNF-like ligand mutein monomer. The invention features methods of producing such TNFSF and TNF-like ligand muteins, pharmaceutical compositions containing such muteins, and methods of using such muteins in cancer immunotherapy, in treating autoimmune and neurological diseases, and in reducing or eliminating the complications and risks of rejection in organ transplantation or tissue or organ repair or regeneration.

The object of the invention is to provide an anaerobic enterobacterium having a higher therapeutic effect on an anaerobic site such as a solid tumor tissue and an ischemic disease site. A bacterium of the genus Bifidobacterium, which is transformed with a plasmid co-expressing two types of heterologous polypeptides and comprising two types of secretory expression cassettes each sequentially comprising a promoter DNA functioning in the bacterium of the genus Bifidobacterium; a DNA encoding a secretory signal peptide; a DNA encoding a heterologous polypeptide; and a terminator DNA functioning in the bacterium of the genus Bifidobacterium, efficiently secretes the two types of heterologous peptides, i.e., two types of antibodies having anticancer effects, outside the bacterial cell.

The object of the invention is to provide an anaerobic enterobacterium having a higher therapeutic effect on an anaerobic site such as a solid tumor tissue and an ischemic disease site. A bacterium of the genus Bifidobacterium, which is transformed with a plasmid co-expressing two types of heterologous polypeptides and comprising two types of secretory expression cassettes each sequentially comprising a promoter DNA functioning in the bacterium of the genus Bifidobacterium; a DNA encoding a secretory signal peptide; a DNA encoding a heterologous polypeptide; and a terminator DNA functioning in the bacterium of the genus Bifidobacterium, efficiently secretes the two types of heterologous peptides, i.e., two types of antibodies having anticancer effects, outside the bacterial cell.

Provided herein are compositions and methods for treating an inflammatory respiratory disorder. Exemplified are compositions comprising interferon-beta of IFN-beta-fusion peptides.

The present invention relates to a modified cytokine of the TNF superfamily, with reduced activity to its receptor, wherein said modified cytokine is specifically delivered to target cells. Preferably, said modified cytokine is a single chain variant of the TNF superfamily, even more preferably, one or more of the chains can-y one or more mutations, resulting in a low affinity to the receptor, wherein said mutant cytokine is specifically delivered to target cells. The targeting is realized by fusion of the modified cytokine of the TNF superfamily to a targeting moiety, preferably an antibody or antibody-like molecule. The invention relates further to the use of such targeted modified cytokine of the TNF superfamily to treat diseases.

The present invention relates to a modified cytokine of the TNF superfamily, with reduced activity to its receptor, wherein said modified cytokine is specifically delivered to target cells. Preferably, said modified cytokine is a single chain variant of the TNF superfamily, even more preferably, one or more of the chains can-y one or more mutations, resulting in a low affinity to the receptor, wherein said mutant cytokine is specifically delivered to target cells. The targeting is realized by fusion of the modified cytokine of the TNF superfamily to a targeting moiety, preferably an antibody or antibody-like molecule. The invention relates further to the use of such targeted modified cytokine of the TNF superfamily to treat diseases.

The present invention relates to a tumor necrosis factor receptor (TNFR) binding protein complex comprising 12 or more N protein ligands (PLs) that specifically bind to the extracellular part of the same TNFR. Preferably, the TNFR binding protein complex binds to the extracellular part of TNFR2. Preferably, the TNFR binding protein complex of the present invention further comprises a two or more polymerization domains (PD).

The present invention relates to a tumor necrosis factor receptor (TNFR) binding protein complex comprising 12 or more N protein ligands (PLs) that specifically bind to the extracellular part of the same TNFR. Preferably, the TNFR binding protein complex binds to the extracellular part of TNFR2. Preferably, the TNFR binding protein complex of the present invention further comprises a two or more polymerization domains (PD).

Described herein are methods, systems, compositions, and kits useful for the diagnosis and/or treatment of a disease or condition in a subject. The present disclosure relates to methods and systems for identifying and stratifying patients suitable for treatment with a modulator of RNASET2, as described herein.