Thomas Jefferson University

Other

Kings College

Robert Korngold

Ziwei Huang

Bradford A Jameson

James M McDonnell

Swati Choksi

Robert Martin Townsend

Hannah J Gould

Brian J Sutton

Andrew J Beavil

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C&#x2014;C' loop of the D1 domain; residues 317-323, the C&#x2014;C&#x2032; loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

Mimetics of CD4 that inhibit immune response

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C-C' loop of the D1 domain; residues 317-323, the C-C&#x2032; loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

CD4-derived peptides that inhibit immune response

Peptides which mimic a loop on the &ggr;-chain that either interact with a cytokine or a &ggr;-chain partner receptor chain of a heterodimeric cytokine receptor are disclosed. The peptides consist of 5-25 amino acids and inhibit signal transduction mediated by cytokine:receptor binding of cytokines that bind to receptors that comprise a &ggr;-chain. Pharmaceutical compositions that comprise the peptides are disclosed. Methods of inhibiting signal transduction mediated by cytokine:receptor binding of cytokines that bind to receptors that comprise a &ggr;-chain, methods of inhibiting cytokine mediated cell growth, proliferation, function or activity, methods of treating patients suffering from a disease disorder or condition characterized by cytokine mediated cell growth, proliferation, function or activity and methods of preventing a condition characterized by cytokine mediated cell growth, proliferation, function or activity are disclosed.

Peptide mimics of the cytokine receptor common &ggr; chain and methods and compositions for making and using the same

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

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4.sup.+ T cell immune responses by identifying compounds that block the interaction of CD4 and class II MHC gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4.sup.+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 500 and 150 that bind to the GFCC'C' portion of the D1 domain of human CD4 lymphocyte cell surface antigen.

Use of CD4-binding small molecules to inhibit immune responses

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

The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4.sup.+ T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4.sup.+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C-C' loop of the D1 domain; residues 317-323, the C-C' loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.

CD-4 derived peptides that inhibit immune responses

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.

Growing community of inventors

Cherry Hill, NJ, United States of America

Robert Korngold