Intercellular adhesion molecules and their binding ligands

Abstract

The present invention relates to intercellular adhesion molecules (ICAM-1) which are involved in the process through which lymphocytes recognize and migrate to sites of inflammation as well as attach to cellular substrates during inflammation. The invention is directed toward such molecules, screening assays for identifying such molecules and antibodies capable of binding such molecules. The invention also includes uses for adhesion molecules and for the antibodies that are capable of binding them.

1 . ICAM-1, or a functional derivative thereof, substantially free of natural contaminants. 
     
     
         2 - 6 . (canceled) 
     
     
         7 . A recombinant DNA molecule capable of expressing ICAM-1 or a functional derivative thereof. 
     
     
         8 . (canceled) 
     
     
         9 . A method for recovering ICAM-1 in substantially pure form which comprises the steps:
 (a) solubilizing ICAM-1 from the membranes of cells expressing ICAM-1, to form a solubilized ICAM-1 preparation,   (b) introducing said solubilized ICAM-1 preparation to an affinity matrix, said matrix containing immobilized antibody capable of binding to ICAM-1,   (c) permitting said ICAM-1 to bind to said antibody of said affinity matrix,   (d) removing from said matrix any compound incapable of binding to said antibody and   (e) recovering said ICAM-1 in substantially pure form by eluting said ICAM-1 from said matrix.   
     
     
         10 - 14 . (canceled) 
     
     
         15 . A method of identifying a non-immunoglobulin antagonist of intercellular adhesion which comprises:
 (a) incubating a non-immunoglobulin agent capable of being an antagonist of intercellular adhesion with a lymphocyte preparation, said lymphocyte preparation containing a plurality of cells capable of aggregating,   (b) examining said lymphocyte preparation to determine whether the presence of said agent inhibits the aggregation of said cells of said lymphocyte preparation; wherein inhibition of said aggregation identifies said agent as an antagonist of intercellular adhesion.   
     
     
         16 . A method for treating inflammation resulting from a response of the specific defense system in a mammalian subject which comprises providing to a subject in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress said inflammation; wherein said anti-inflammatory agent is selected from the group consisting of: an antibody capable of binding to ICAM-1; a fragment of an antibody, said fragment being capable of binding to ICAM-1; ICAM-1; a functional derivative of ICAM-1; and a non-immunoglobulin antagonist of ICAM-1. 
     
     
         17 - 44 . (canceled) 
     
     
         45 . A method of suppressing the metastasis of a hematopoietic tumor cell, said cell requiring a functional member of the LFA-1 family for migration, which method comprises providing to a patient in need of such treatment an amount of an anti-inflammatory agent sufficient to suppress said metastasis; wherein said anti-inflammatory agent being selected from the group consisting of: an antibody capable of binding to ICAM-1; a fragment of an antibody, said fragment being capable of binding to ICAM-1; ICAM-1; a functional derivative of ICAM-1; and a non-immunoglobulin antagonist of ICAM-1. 
     
     
         46 - 53 . (canceled) 
     
     
         54 . A method of diagnosing the presence and location of inflammation resulting from a response of the specific defense system in a mammalian subject suspected of having said inflammation which comprises:
 (a) administering to said subject a composition containing a detectably labeled binding ligand capable of identifying a cell which expresses ICAM-1, and   (b) detecting said binding ligand.   
     
     
         55 - 68 . (canceled) 
     
     
         69 . A pharmaceutical composition comprising:
 (a) an anti-inflammatory agent selected from the group consisting of: an antibody capable of binding to ICAM-1; a fragment of an anti-body, said fragment being capable of binding to ICAM-1; ICAM-1; a functional derivative of ICAM-1; and a non-immunoglobulin antagonist of ICAM-1, and   (b) at least one immunosuppressive agent selected from the group consisting of: dexamethasone, azathioprine and cyclosporin A.   
     
     
         70 . (canceled)