The present invention relates to uses and methods comprising one or more RANK/RANKL antagonists or of a pharmaceutical composition comprising one or more RANK/RANKL antagonists and a pharmaceutically acceptable carrier for treating neuromuscular disorders, non-genetic myopathies, or genetic myopathies; maintaining and/or preserving the excitation:contraction:relaxation coupling; reducing loss of muscle strength associated with neuromuscular disorders, non-genetic myopathies or genetic myopathies; reducing the loss of muscular strength associated with skeletal or cardiac muscle disuse, diseases and aging; or regulating skeletal or cardiac muscle disuse, diseases and/or aging in a patient in need thereof. The present invention also relates to combinations and compositions comprising one or more RANK/RANKL antagonists and to methods for identifying candidate compounds.

An antibody or an antigen-binding fragment thereof capable of specifically binding to TNFR2, the antibody or the antigen-binding fragment thereof is capable of regulating the function of immune cells and may be used as a medicament to treat diseases related to immune-related disorders, such as tumors.

Described are agonistic TNFR2 polypeptides, such as antibodies and antigen-binding fragments thereof, and the use of these polypeptides to stimulate the proliferation of regulatory T cells (Treg cells) and/or myeloid-derived suppressor cells (MDSCs), as well as to inhibit the function of, reduce the proliferation of, and/or directly kill, T effector cells, such as CD8+ T effector cells. The polypeptides, such as antibodies and antigen-binding fragments thereof, of the disclosure can be used, for example, to suppress autoimmunity and inflammation, as well as to promote the protection, healing, preservation, and/or regeneration of a wide variety of tissues and organs, such as tissues and organs containing TNFR2+ cells.

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.

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. Anew assay for identifying compounds with this mechanism of action is also disclosed.

Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.

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 agonistic TNFR2 antibodies and antigen-binding fragments thereof and encompasses the use of these antibodies as therapeutics to promote the proliferation of regulatory T cells (T-reg) for the treatment of immunological diseases. Antibodies of the invention can be used to potentiate the T-reg-mediated deactivation of self- and allergen-reactive T- and B-lymphocytes, and can thus be used to treat a wide variety of indications, including autoimmune diseases, allergic reactions, asthma, graft-versus-host disease, and allograft rejection, among others.

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.