A bispecific antibody specifically binding to the two targets human CD3 and human BCMA, wherein the variable domains of one antibody portion are replaced by each other, and characterized in that the binding of said antibody is not reduced by APRIL and not reduced by BAFF, said antibody does not alter APRIL-dependent NF-B activation, BAFF-dependent NF-B activation, and does not alter NF-B activation without BAFF and APRIL is useful as a therapeutic agent.

A new, stable trimeric TNF? structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNF?/TNFR1 interaction. Membrane-bound TNF? is not affected in its ability to signal through TNFR2, and thus the new structure of TNF? may be used in therapies which do not significantly raise the risk of infection or malignancy.

An antibody specifically binding to human BCMA, characterized in that the binding of said antibody is not reduced by APRIL and not reduced by BAFF, said antibody does not alter APRIL-dependent NF-B activation, BAFF-dependent NF-B activation, and does not alter NF-B activation without BAFF and APRIL is useful as a therapeutic agent.

The invention is in the field of TNF signalling. Compounds have been identified which are capable of modulating signalling of TNF trimers through receptors. Methods of identifying such compounds are therefore provided. The compounds themselves have utility in therapy.

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Antibodies which selectively bind to complexes of such compounds with TNF superfamily members are disclosed. These antibodies may be used to detect further compounds with the same activity, and as target engagement biomarker.

It has been demonstrated that certain compounds bind to TNF and stabilise a conformation of trimeric TNF that binds to the TNF receptor. Accordingly, these compounds can be used as modulators of TNF. A new assay for identifying compounds with this mechanism of action is also disclosed.

Provided herein are diagnostic antibodies that bind to glucocorticoid-induced tumor necrosis factor receptor (GITR). Such antibodies are useful for methods of detecting the expression of GITR in biological samples, for example, tumor tissue, and identifying a cancer patient likely to respond to anti-GITR immunotherapy or predicting whether a cancer patient will respond to anti-GITR immunotherapy.

The invention provides models of various conditions including but not limited to intestinal inflammation and/or fibrosis, inflammatory bowel disease, colitis, acute colitis, and chronic colitis, and methods of using such models for designing, screening and developing therapeutics for those conditions. The invention also provides methods, compositions, and kits for treating those conditions.

A method for predicting risk of gestational diabetes mellitus (GDM) in a pregnant individual includes measuring one or more biochemical markers in a blood sample obtained from the pregnant individual to determine one or more biomarker levels, where the one or more measured biochemical markers includes at least one of PAI-2 and sTNFR1, identifying, for each of the one or more measured biochemical markers, a difference between the measured biomarker level and a corresponding predetermined control level, and, responsive to the identifying, determining a prediction corresponding to a relative risk of the pregnant individual having or developing GDM.