Compounds having formula I, ##STR00001##
or pharmaceutically acceptable salts, hydrates or N-oxides thereof are provided and are useful for binding to CXCR7, and treating diseases that are dependent, at least in part, on CXCR7 activity. Accordingly, the present invention provides in further aspects, compositions containing one or more of the above-noted compounds in admixture with a pharmaceutically acceptable excipient.

The present disclosure is directed to methods and kits of use of serum biomarkers, including CXCL10, CXCL13, and/or sCD27, for predicting and evaluating therapeutic response to TNF inhibitor therapy in a patient in need thereof.

The present invention provides a prophylactic agent, onset-suppressing agent, or therapeutic agent for progressive immune demyelinating diseases comprising, as an active ingredient, a substance capable of suppressing or inhibiting production of prolactin.

The present invention relates to a method, in particular an in vitro method, for specifically identifying the C-X-C motif chemokine receptor 3 (CXCR3) subpopulation of immune cells in a sample from a mammal comprising immune cells, in particular at least one of CD8+ effector and memory T cells, T helper (Th)1 cells and natural killer T (NKT) cells, comprising analyzing epigenetic modifications/properties of (including the methylation status) of at least one CpG position in the mammalian gene region for CXCR3 according to SEQ ID No. 1, wherein a demethylation or lack of methylation of said of at least one CpG position in said gene region is indicative for said CXCR3 specific subpopulation of immune cells in said sample, when compared to other immune cells, in particular for at least one of CD8+ effector and memory T cells, T helper (Th)1 cells and natural killer T (NKT) cells. The analyses according to the invention can identify the above cells on an epigenetic level and distinguish them from all other cells in complex samples, such as, for example, other blood or immune cells. The present invention furthermore provides an improved method for quantifying the above cells, in particular in complex samples. The method can be performed without a step of purifying and/or enriching cells, preferably in whole blood and/or non-trypsinized tissue.

An in vitro co-culture system comprising cancer-associated fibroblasts (CAFs) and cancer cells for producing and maintaining cancer stem cells and uses thereof for identifying agents capable of reducing cancer cell stemness. Also disclosed herein are a paracrine network through which CAFs facilitate production and/or maintenance of cancer stem cells and the use of components of such a paracrine network for prognosis purposes and for identifying cancer patients who are likely to respond to certain treatment.

Provided are a refractory asthma prophylactic/therapeutic agent screening method, and a refractory asthma prophylactic/therapeutic agent. This refractory asthma prophylactic/therapeutic agent screening method uses at least one indicator selected from the group consisting of: inhibited activity of the CXCL2 protein or the CXCR2 protein; suppressed expression of the CXCL2 gene or the CXCR2 gene; and suppressed expression of the CXCL2 protein or the CXCR2 protein.

A method of treating acute myeloid leukemia (AML), including the steps of (i) measuring a density of blast cells in the peripheral blood and the bone marrow of a subject with AML; (ii) administering to the subject a CXCR4 antagonist; and (iii) administering to the subject a therapeutically effective amount of the CXCR4 antagonist and a therapeutically effective amount of a chemotherapeutic agent, if the blast cell density in the peripheral blood is less than 10% of the total peripheral white blood cells, or at least five-fold lower than the blast cell density in the bone marrow, or at least two-fold higher one day or more following step (ii).

The present invention provides a biomarker for predicting effectiveness for autoimmune disease treatment, a diagnostic kit, and a use for treatment. More particularly, the present invention provides a biomarker for predicting the effectiveness of mesenchymal stem cells (MSC) comprising the chemokine receptor CXCR3 for autoimmune disease treatment; a biomarker comprising the chemokine CXCL10 for predicting the prognosis of autoimmune disease treatment; a diagnostic kit comprising an agent capable of measuring the expression of the biomarker; and a pharmaceutical composition for prevention or treatment of an autoimmune disease, which comprises mesenchymal stem cells having an upregulated expression level of the chemokine receptor CXCR3.

The present invention provides novel pan-cancer T cell exhaustion regulators. CXCR6 expressed in CD8+ T cells was specifically identified as regulating anti-tumor immunity. Modulating CXCR6-CXCL16 interaction is useful in modulating anti-tumor immunity. The identified genes may be modulated in T cells for use in adoptive cell transfer. The identified genes may be modulated in vivo.

The disclosure provides antibody constructs that can reversibly bind to biological or chemical target analytes. Upon target analyte binding, the antibody construct can change its conformational state to produce a detectable readout. An antibody construct can be a single-antibody construct or a dual-antibody construct.