Recombinant antibodies that specifically bind to IL-15 as well as a complex of IL-15 and the IL-15 Receptor-alpha are provided. The antibodies inhibit immune cell proliferation, and are capable of use in the treatment of any autoimmune or inflammatory disease or condition where IL-15 is dysregulated, including Celiac disease.

Methods and compositions related to the selective, specific disruption of multiple ligand-receptor signaling interactions, such as ligand-receptor interactions implicated in disease, are disclosed. These interactions may involve multiple cytokines in a single receptor family or multiple ligand receptor interactions from at least two distinct ligand-receptor families. The compositions may comprise polypeptides having composite sequences that comprise sequence fragments of two or more ligand binding sites. The methods and compositions may involve sequence fragments of two or more ligand binding sites that are arranged to conserve the secondary structure of each of the ligands from which the sequence fragments were taken.

The invention provides compositions, formulations, and methods for treatment of malignancies via activation of an inflammatory response in the subject. Such compositions, formulations, and methods for are preferably used in conjunction with other therapies for the treatment and/or management of malignancies, e.g., chemotherapy and/or radiation. The invention also provides methods of monitoring immune activation in subjects with malignancies.

Recombinant antibodies that specifically bind to IL-15 as well as a complex of IL-15 and the IL-15 Receptor-alpha are provided. The antibodies inhibit immune cell proliferation, and are capable of use in the treatment of any autoimmune or inflammatory disease or condition where IL-15 is dysregulated, including Celiac disease.

The present disclosure provides methods and compositions that find use in facilitating a diagnosis of inflammatory liver disease in a subject. The methods and compositions generally involve detection of eotaxin-3 (E3) levels, either alone or with levels of eotaxin-1 (E1), and optionally, with levels of CCL22 and, further optionally, with levels of IL15. These levels can be used to facilitate a diagnosis of a liver disease of at least one of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), and/or to facilitate a differential diagnosis between AIH, PBC, and PSC. The methods and compositions of the present disclosure also find use in facilitating treatment decisions for a subject.

The invention provides methods of increasing the efficacy of a T cell therapy in a patient in need thereof. The invention includes methods of identifying a patient who would respond well to a T cell therapy or conditioning a patient prior to a T cell therapy so that the patient responds well to a T cell therapy. The conditioning involves administering one or more preconditioning agents prior to a T cell therapy and identifying biomarker cytokines prior to administering a T cell therapy.

The present invention relates to antibodies binding IL-15, in particular humanized antibodies. In particular, the anti-IL-15 antibodies according to the invention are able to neutralize IL-15 activity and are useful in the prevention and/or treatment of an autoimmune disease and/or inflammatory disorder, a malignancy, transplant rejection, metabolic condition and/or an infectious disease caused by parasitic, viral or bacterial pathogens.

In various embodiments, provided are immune response signatures that can be used for the diagnosis, monitoring, and treatment of long-term diseases and inflammatory disorders caused by viral infections. In some embodiments, the viral infection is SARS-CoV-2 infection. In some embodiments, the long-term disease is post-acute sequelae of SARS-CoV-2 infection (PASC).

Provided is a long-acting IL-15 fusion protein, comprising a monomeric fragment Fc, an IL-15 receptor ? sushi domain, and an IL-15 functional fragment. The IL-15 fusion protein has a higher yield than an Fc fusion protein, and can reduce the number of Treg cells in a tumor tissue, effectively activate an immune system to kill tumor cells, and improve the in vivo tumor inhibitory effect of IL-15.

The present invention includes methods, systems, and kits, for identifying and modifying the treatment of a systemic lupus erythematosus (SLE) patient prior to the presence of autoantibodies, comprising: (a) obtaining a dataset representing protein expression level values for cytokines and molecules; (b) assessing the dataset for protein expression levels of at least one innate serum mediator; (c) assessing the dataset for protein expression levels of at least one adaptive serum mediator; and (d) determining the likelihood that the patient will develop SLE prior to the onset of autoantibodies when compared to a control.