Thomas Jefferson University

Temple University

Drexel University

Kings College

Bradford A Jameson

Robert Korngold

James M McDonnell

Robert W Colman

Swati Choksi

Harlan N Bradford

Renato L Baserga

Ziwei Huang

Hannah J Gould

Ross Albert

Mariadele Noe

Harold Carter Davidson

Andrew J Beavil

Anna A Tretiakova

Brian J Sutton

The present invention relates to the discovery that signaling via a serotonin type 1B, 2, 4 and 6 receptor is important in T cell activation such that inhibiting such signaling can be used to modulate the immune response. This immunomodulation is useful for the treatment of immune diseases or conditions, and for the development of potential therapeutics for such diseases or conditions. It has been further discovered that, in cells proceeding through the cell cycle process, inhibition of serotonin signaling inhibits the process and induces apoptosis and morphological changes to a cell. These effects of inhibiting serotonergic signaling can be useful for effecting selective cell killing and for identifying compounds that inhibit the signaling.

Immunomodulation and effect on cell processes relating to serotonin family receptors

Compounds that inhibit CD8 mediated T cell activation and that have a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 38-46 and/or 53-56 and/or 60-67 and pharmaceutical compositions comprising such compounds are disclosed. Methods of inhibiting activation of a human T cell are disclosed. The methods comprise contacting a T cell with a compound that inhibits CD8 mediated T cell activation and that has a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 38-46 and/or 53-56 and/or 60-67. Methods of treating an individual suspected of suffering from or susceptible to graft versus host disease and/or organ rejection are disclosed. The methods comprise administering an effective amount of a compound that inhibits CD8 mediated T cell activation and that has a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 34-46 and/or 53-56 and/or 60-67.

CD8 antagonists

TNF.alpha. antagonist compounds and methods of using the same are disclosed. The compounds comprise a molecular surface that is substantially similar to at least one molecular surface of human TNF.alpha.. The compounds bind to TNF receptors but do not produce the same biological effect as that which occurs when TNF.alpha. binds to a TNF receptor. Methods of inhibiting tumor necrosis factor activity are disclosed. The methods comprise the step of contacting tumor necrosis factor alpha with a TNF.alpha. antagonist. Methods of treating individuals suspected of suffering from or being susceptible to a disease or disorder mediated by tumor necrosis factor-alpha activity are disclosed. The methods comprise the step of administering to said individual a therapeutically effective amount of a TNF.alpha. antagonist.

Tumor necrosis factor inhibitors

IgE antagonists

Compounds which display a surface similar to the surface presented by one of five distinct lateral domains of CD4 are disclosed. Methods of treating individuals suspected of suffering from or susceptible to conditions characterized by an undesired immune response comprising administering to the individual at least one compound which mimics a portion of the lateral surface of the CD4 glycoprotein are disclosed.

Compounds that inhibit T cell proliferation and methods using the same

Synthetic peptide analogs of human kininogen are provided which are conformationally restricted by means of intramolecular bonding. The peptides mimic the biological activity of human kininogen by inhibiting the activity of the biologically significant protease, calpain. The peptides are designed by means of an equilibrium conformational model of the kininogen heavy chain.

Calpain-inhibiting peptide analogs of the kininogen heavy chain

Compounds that inhibit CD8 mediated T cell activation and that have a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 53-56 and/or 60-67 and pharmaceutical compositions comprising such compounds are disclosed. Method of inhibiting activation of a human T cell are disclosed. The methods comprise contacting a T cell with a compound that inhibits CD8 mediated T cell activation and that has a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 53-56 and/or 60-67. Methods of treating an individual suspected of suffering from or susceptible to graft versus host disease and/or organ rejection are disclosed. The methods comprise administering an effective amount of a compound that inhibits CD8 mediated T cell activation and that has a molecular surface that corresponds to the molecular surface of human CD8 at amino acids 53-56 and/or 60-67.

Peptides that inhibit T cell activation and methods of using the same

Compounds that inhibit T cell proliferation and methods for using the

Short peptides which function as analogs of IGF-1 are provided. These peptides abolish the proliferation of cells at nanogram concentrations. The peptides are non-toxic, and the inhibitor effect is reversible. The use of these peptides, because of their low toxicity and high efficiency, holds promises for treatment of a variety of human conditions, including prevention of restenosis of the coronary arteries after angioplasty, treatment of human neoplasia such as cancer of the prostate, treatment of tumors in pleural and peritoneal cavities and brain metastases, treatment of other abnormalities of cell growth in human beings, treatment of smooth muscle cell hyperplasia in asthma, treatment to promote burn and wound healing, and purging bone marrow from highly proliferating cells.

IGF-1 analogs

Growing community of inventors

Philadelphia, PA, United States of America

Bradford A Jameson