Method of reducing tissue damage at an inflammatory site using a monoclonal antibody

• US 4,935,234 A
• Filed: 03/07/1988
• Issued: 06/19/1990
• Est. Priority Date: 06/11/1987
• Status: Expired due to Term

• Current Assignee: Dana-Farber Cancer Institute, University of Michigan
• Original Assignee: Dana-Farber Cancer Institute
• Inventors: Simpson, Paul J., Todd, Robert F. III, Scholossman, Stuart F., Griffin, James D., Lucchesi, Benedict R.
• Primary Examiner(s): Draper, Garnette
• Assistant Examiner(s): Kushan, Jeff
• Application Number:
  US07/165,025
• Time in Patent Office: 834 Days
• Field of Search: 424/85.8, 530/387, 530/808, 530/382, 530/828, 435/240.27
• US Class Current: 424/153.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: C07K 16/2845 against integrin beta2-subunit-containing molecules, e.g. CD11, CD18
• CPC Class Codes: Y10S 530/806 Antigenic peptides or proteins
• CPC Class Codes: Y10S 530/808 Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products

Abstract

A method of reducing tissue injury in humans or other animal species using a monoclonal antibody to inhibit specific phagocyte functions. The monoclonal antibody is selected to bind to phagocytic leukocytes for the purpose of inhibiting migration to an inflammatory site in the body and to inhibit the adhesion and spreading of activated leukocytes reaching such an area and then, block release of toxic substances by these cells. The monoclonal antibody is administered in vivo prior or early in the course of an experience leading to an injurious inflammatory response such as can result from restoration of myocardial blood flow interrupted by an acute coronary thrombosis.

Claims

1. A method of treating a human or animal host with the intent of reducing tissue damage occurring at an inflammatory site in any part of the body of a host experiencing a phagocyte-mediated inflammatory condition, said method comprising:

administering in vivo a monoclonal antibody which will bind specifically only to the CD11b part of the CD11/CD18 glycoprotein of the Mo1 antigen expressed on the surface of granulocytes and other phagocytic cells and will inhibit the CD11/CD18 adhesion dependent cellular interactions of such cells reflecting their immonoloical inflammatory response function which contributes to such damage.

2. The method of claim 1 in which said monoclonal antibody binds to an epitope on the CD11b, 155,000 dalton molecular weight peptide molecule of the Mo1 glycoprotein expressed on the surface of such cells.

3. The method of claim 1 in which said inflammatory site is located at the vascular endothelial cell interface or subcellular matrix of a body part.

4. The method of claim 1 in which said inflammatory site is in endothelial tissue of a body part.

5. The method of claim 1 in which said inflammatory site is in a joint of the body part.

6. The method of claim 1 in which said inflammatory site is developed from a myocardial infarct condition.

7. The method of claim 1 in which the monocolonal antibody is administered intravenously at a selected time period prior to or during said inflammatory condition.

8. The method of claim 1 in which said monoclonal antibody binds the Mo1 glycoprotein of neturophils.

9. A method of reducing myocardial inflammation damage in a human patient experiencing acute coronary thrombosis, said patient having been treated initially either medically or surgically to renew myocardial blood flow at the inflammatory site, said method comprising supplying intravenously at least prior to such blood flow renewal a quantity of a murine monoclonal antibody which binds specifically only an epitope expressed on CD11b part of CD11/CD18 glycoprotein of the Mo1 surface antigen of neutrophils whereby to inhibit the adhesive-dependent cellular interactions of the neturophils at said site reflecting their immunological response function whereby to decrease the deleterious action of neturophils at said site.

10. A method of treating a human host with the intent of reducing tissue damage occurring at an inflammatory site in the body of the human experiencing an inflammatory condition, said method comprising:

infusing into the body prior to or during said inflammatory condition a quantity of murine monoclonal antibody which will bind specifically only to an epitope expressed on the CD11b, 155,000 dalton molecular weight peptide of the Mo1 antigen expressed on the surface of neutorphils and will inhibit the CD11/CD18 adhesion dependent intercellular reactions of neturophils reflecting their immunological response function which contributes to such damage.