The present disclosure relates to anti-IL-27 antibodies, and antigen-binding portions thereof. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the antibodies or antigen-binding portion thereof. The disclosure also relates to methods for detecting IL-27 in, for example, a subject or a sample.

The present invention relates to the use of the Chemokine (C—C motif) ligand 20 (CCL20) as a biomarker to stratify or identify populations of patients suffering from interleukin-23 (IL23)-mediated diseases (e.g., Crohn's disease) responsive to treatment with an, anti-IL23 antagonist (including, e.g., anti-IL23 antibodies). Levels of CCL20 above or below a predetermined threshold can be used, for example, (i) to determine whether a patient with an IL23-mediated disease or disorder such a Crohn's disease is eligible or non-eligible for treatment with a therapeutic agent, (ii) to determine whether treatment with a certain agent should be commenced, suspended, or modified, (iii) to diagnose whether the IL23-mediated disease is treatable or not treatable with a specific therapeutic agent, or (iv) to predict the outcome of treating the IL23-mediated disease with a specific therapeutic agent. CCL20 can be used in combination with other IL23 pathway biomarkers such as IL22 and/or lipocalin-2 (LCN2).

The invention includes compositions comprising a therapeutic agent that decreases the population of pathological CD4g13 T cells, g13Th1 or g13Th2, in a subject and compositions comprising a therapeutic agent that increases the population of protective CD4g13 T cells, g13Th1 or g13Th2, in a subject. The invention also includes methods for treating an inflammatory or autoimmune disease in a subject by administering to the subject an effective amount of a therapeutic agent that increases the population of protective CD4g13 T cells, methods for detecting a protective or pathological immune response and methods for stimulating a protective CD4g13 T cell-mediated immune response to a cell population or a local tissue or organ in a subject in need thereof. The invention further includes a kit for diagnosing a pathological or protective g13Th1 or g13Th2 T cell responses in a subject.

An antibody or an antigen-binding fragment can specifically recognize IL-11 thereof. The antibody contains CDR sequence(s) selected from at least one of the following or an amino acid sequence having at least 95% identity thereto: heavy chain variable region CDR sequences: SEQ ID NOs: 1-33 and light chain variable region CDR sequences: SEQ ID NOs: 34-66. The antibody can specifically target and bind to IL-11, so as to block binding of IL-11 and an IL-11 receptor.

The present invention relates to a conjugate that specifically targets a calcineurin inhibitor to T cells, such as Th17 cells, for use in a method for the treatment of an inflammatory disease. The invention also relates to a method for treating an inflammatory disease by administering a conjugate that specifically targets a calcineurin inhibitor to T cells, such as Th17 cells. In addition, the invention relates to a method for identifying a subject likely to be resistant to steroid treatment, as well as a subject likely to benefit from treatment with a calcineurin inhibitor.

Renal Cell Carcinoma (RCC) encompasses a heterogeneous group of cancers derived from renal tubular epithelial cells and has a worldwide mortality. However, mortality rates have barely improved over the last 20 years. Novel biomarkers and biomarkers are thus urgently required for this cancer. The inventors have devised a strategy to produce mouse cancer cell lines of progressively enhanced aggressiveness and specialization. The mouse renal cancer cell line RENCA was serially passaged in vivo using multiple implantation strategies designed to replicate different aspects of primary tumour growth and metastasis. Transcriptomic and epigenomic data has been acquired for the derived cell lines and primary analyses have been performed. The inventors then selected plurality of genes with no reported role in RCC which were upregulated in their specialized cell lines, and checked their relevance in patient data and clinical samples. This approach contributes to identify 4 serum biomarkers, namely IL-34, SAA2, PONL1 and CFB that are suitable for predicting survival time in patients suffering from RCC. The inventors also validated that the 4 proteins are also biotargets for the treatment of RCC.

The invention provides methods of identifying schizophrenia patients at risk for relapse. The invention also provides methods of early detection of schizophrenic relapse. The disclosed methods use monitoring of a subset of symptoms and/or one or more biomarkers. The symptom severity can be assessed using the Positive and Negative Syndrome Scale (PANSS) parameters. The methods of the invention can be used to provide early intervention to decrease or prevent relapse in schizophrenia patients.

A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising administering the treatment compound to the subject having the cancer; obtaining a sample from the subject; determining the level of a biomarker in the sample from the subject; and diagnosing the subject as being likely to be responsive to the treatment compound if the level of the biomarker in the sample of the subject changes as compared to a reference level of the biomarker; wherein the treatment compound is Compound 1, Compound 2, or Compound 3.

The present invention provides means and methods for treating Interleukin 18 (IL-18)-associated diseases and disorders. In particular, the present invention discloses antibodies specific for free IL-18 and IL-18 Binding Protein (IL-18BP) for use in such treatments and for the diagnosis of the indications.

The present invention provides compositions and methods for detecting components of the inflammasome in a sample from a subject as markers for brain injuries such as multiple sclerosis, stroke or traumatic brain injury. Methods of using such inflammasome markers to determine prognosis, direct treatment and monitor response to treatment for the subject with a brain injury such as multiple sclerosis, stroke, mild cognitive impairment or traumatic brain injury are also described.