Methods and Compositions for Treatment of Human Immunodeficiency Virus Infection with Conjugated Antibodies or Antibody Fragments

Abstract

The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4/D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent.

What is claimed is: 
     
         1 . A method for treating HIV infection in a subject, comprising:
 a) administering to the subject a bispecific antibody or fragment thereof, the bispecific antibody comprising one or more binding sites specific for an HIV surface envelope antigen and one or more binding sites for a carrier;   b) administering to the subject a carrier conjugated to a therapeutic agent, wherein the therapeutic agent is a fusion inhibitor, said administration of said carrier effective to reduce, eliminate or prevent HIV infection or to prevent the intercellular transmission of HIV to uninfected cells in the subject.   
     
     
         2 . The method of  claim 1 , further comprising administering a clearing agent to the subject. 
     
     
         3 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         4 . The method of  claim 1 , wherein the antibody or fragment is a chimeric, humanized or human antibody or fragment. 
     
     
         5 . The method of  claim 1 , wherein the antibody or fragment and carrier are administered to the subject after the subject is treated with anti-retroviral therapy. 
     
     
         6 . The method of  claim 1 , wherein the bispecific antibody or fragment comprises at least one scFv, Fab, Fab′, F(ab) 2 , F(ab′) 2 , Fv, sFv, scFv-Fc fusion, single chain antibody, diabody, triabody or tetrabody. 
     
     
         7 . The method of  claim 1 , wherein the bispecific antibody or fragment comprises at least one P4/D10 antibody or fragment. 
     
     
         8 . The method of  claim 1 , wherein the carrier comprises one or more HSG (histamine-succinyl-glycine) moieties and the bispecific antibody or fragment binds to HSG. 
     
     
         9 . The method of  claim 8 , wherein the bispecific antibody or fragment comprises one or more 679 antibodies or antibody fragments that bind to HSG. 
     
     
         10 . The method of  claim 1 , wherein the carrier is DOTA-D-Cys(3-SP-Gly-20-O-SN38)-D-Ala-D-Lys(HSG)-D-Tyr-D-Lys(HSG)-NH 2  (IMP-411). 
     
     
         11 . The method of  claim 1 , wherein the bispecific antibody or fragment comprises a dock and lock (DNL) structure.