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.

An agent capable of binding to CLEVER-1 in an individual can be used in activating macrophages to switch their phenotype from M2 macrophages into M1 macrophages. The invention relates to methods for utilizing the macrophages ability to switch their phenotype. In one aspect, the invention relates to a method for estimating of the efficacy of anti-CLEVER-1 therapy by monitoring a modulation of M2 macrophages into M1 macrophages, when an agent capable of binding to CLEVER-1 is administered in a patient, wherein an increased TNF-alpha secretion or HLA-DR expression is indicative of modulation of M2 macrophages into M1 macrophages.

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. Accordingly, these compounds can be used as modulators of TNF. A new assay for identifying compounds with this mechanism of action is also disclosed.

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.

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.

The present invention provides a method of aiding the differential diagnosis of haemorrhagic stroke, ischemic stroke and a transient ischemic attack in a patient who has suffered or is suffering a stroke. The method comprises: (i) determining the concentration of the biomarkers VCAM-1, GFAP and CRP in an ex vivo sample obtained from the patient; and (ii) establishing the statistical significance of the concentration of the biomarkers. Optionally, the method further comprises steps of (iii) determining the concentration of the biomarkers IL-6 and sTNFR1 in an ex vivo sample obtained from the patient; (iv) determining the gender of the patient; and (v) establishing the statistical significance of the concentration of the five biomarkers, in conjunction with the patient's gender. The present invention also provides substrates comprising probes for VCAM-1, GFAP and CRP for use in a method for aiding the differential diagnosis of stroke.

Methods and kits for screening, diagnosing, detecting or predicting a patient outcome/risk variable for a lung transplant recipient after transplant or an EVLP outcome by measuring biomarker levels of one or more biomarkers selected from IL-6, IL-8, sTNFR1 and sTREM-1 in EVLP perfusate are described. The methods involve for example, i. obtaining one or more test EVLP perfusate samples of a donor lung; ii. determining in one or more test EVLP perfusate sample of a donor lung, a polypeptide level of one or more biomarkers selected from IL-8, IL-6, sTNFR1 and sTREM-1; and iii. a) comparing the polypeptide level of the one or more biomarkers in the perfusate sample with a control or cut-off level, wherein the differential level is indicative of outcome/risk of after transplant or of an EVLP outcome; or b) using the polypeptide level of one or several of the one or more biomarkers in combination, as part of an algebraic calculation of outcome/risk.

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.