Research Corporation Technologies, Inc.

Boston University

Los Angeles Biomedical Research Institute at Harbor-ucla Medical Center

Harbor-ucla Research and Education Institute

William W Cruikshank

David M Center

Hardy Kornfeld

Terry J Smith

This invention provides methods and compositions for preventing post-surgical adhesion formation based on use of an interleukin-16 (IL-16) antagonist, including an IL-16 antagonist peptide and/or an IL-16 antagonist antibody.

Methods and compositions for preventing adhesion

The invention provides a method of reducing the severity of an autoimmune condition associated with T-lymphocyte infiltration. The invention also provides a method of diagnosing or predicting the susceptibility to an autoimmune disease associated with fibroblast mediated T-lymphocyte infiltration. Methods of identifying a substance capable of modulating T-lymphocyte recruitment associated with an autoimmune condition also are provided.

Diagnosis and therapy of antibody-mediated inflammatory autoimmune disorders

The present invention describes diagnosis and treatment of antibody-mediated inflammatory auto-immune diseases. The biochemical mechanisms underlying such disorders are described as characteristic molecular markers and antibody-mediated ligand-receptor interactions. Specifically, the activation of T-cells by disease specific IgG binding to the IGF-1 receptor is shown to underlie thyroid associated ophthalmopathy associated with Graves' disease and rheumatoid arthritis. Diagnostics for detection of disease are provided, as are therapeutics based on the determination of the mechanisms underlying a particular pathology.

Diagnosis and therapy of antibody-mediated inflammatory auto-immune disorders

The present invention has found that a series of peptides having sequences that substantially correspond to specific regions of the C-terminus of IL-16 can inhibit the activity of IL-16. The present invention has demonstrated that such IL-16-inhibiting peptides can be as short as 4 amino acids in length. Based on these discoveries, the present invention provides IL-16 antagonist peptides and the use thereof for the treatment of IL-16 mediated disorders such as certain inflammatory diseases.

Methods of treatment using IL-16 antagonist peptides

The present invention has found that a series of peptides having sequences that substantially correspond to specific regions of the C-terminus of IL-16 can inhibit the activity of IL-16. The present invention has demonstrated that such IL-16-inhibiting peptides can be as short as 4 amino acid in length. Based on these discoveries, the present invention provides IL-16 antagonist peptides and the use thereof for the treatment of IL-16 mediated disorders such as certain inflammatory diseases.

Antibodies against IL-16 antagonist peptides

In accordance with the present invention, novel IL-16 antagonists, preferably peptides derived from CD4, have been isolated and synthesized. These peptides possess IL-16 antagonistic properties including the ability to selectively bind to IL-16 and inhibit IL-16-mediated biological activity. The peptides comprise specific portions of the native human CD4 receptor and variations thereof and therefore are non-immunogenic when administered to humans. The present invention also provides compositions containing at least one IL-16 antagonist peptide which can inhibit, suppress or cause the cessation of at least one IL-16-mediated biological activity in mammals, including humans. The present invention provides a method and composition for treating inflammation associated with disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease (IBD) and systemic lupus (SLE) in mammals such as, for example, humans.

IL-16 antagonists

IL-16 antagonist peptides and DNA encoding the peptides

The present invention describes a method to detect connective tissue pathologies associated with Graves' disease ophthalmopathy and other antibody mediated inflammatory autoimmune diseases. The detection method comprises obtaining a sample from a patient suffering from an antibody-mediated inflammatory autoimmune disorder and measuring Interleukin 16 (IL-16) or RANTES produced by thyroid associated ophthalmopathy fibroblasts to indicate the presence or severity.

Detection of antibody mediated inflammatory auto-immune disorders

The present invention has found that a series of peptides having sequences that substantially correspond to specific regions of the C-terminus of IL-16 can inhibit the activity of IL-16. The present invention has demonstrated that such IL-16-inhibiting peptides can be as short as 4 amino acids in length. Based on these discoveries, the present invention provides IL-16 antagonist peptides and the use thereof for the treatment of IL-16-mediated disorders such as certain inflammatory diseases.

Purified DNA encoding LCF and the recombinant proteins expressed from such DNA are disclosed. In addition, the invention provides methods for suppressing an LCF-CD4 interaction and screening candidate LCF agonists or antagonists. The invention also provides compositions and methods useful for stimulating proliferation of CD4+ T-cells in a mammal.

Lymphocyte chemoattractant factor

Disclosed is a substantially pure antibody which specifically binds a LCF polypeptide and methods of using such antibodies.

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Westford, MA, United States of America

William W Cruikshank