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 administering to the subject an anti-gp120 antibody conjugated to a cytotoxic drug, wherein exposure to the conjugated antibody is effective to reduce HIV infection or to limit the intercellular transmission of HIV to uninfected cells. 
     
     
         2 . The method of  claim 1 , wherein the drug is doxorubicin. 
     
     
         3 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         4 . The method of  claim 3 , wherein the antibody is a chimeric, humanized or human antibody or fragment. 
     
     
         5 . The method of  claim 4 , wherein the conjugated antibody is administered to the subject after a known or potential infection with HIV. 
     
     
         6 . The method of  claim 5 , wherein the time period between known or potential infection and administration of the conjugated antibody to the subject is less than 1 hour, 1 to 5 hours, less than 12 hours, 1 day or less, 2 days or less, 1 week or less, or 1 month or less. 
     
     
         7 . The method of  claim 3 , wherein the conjugated antibody is administered to the subject after the subject is treated with anti-retroviral therapy (ART). 
     
     
         8 . The method of  claim 1 , wherein the drug is aplidin, azaribine, anastrozole, azacytidine, bleomycin, bortezomib, bryostatin-1, busulfan, calicheamycin, camptothecin, 10-hydroxycamptothecin, carmustine, celebrex, chlorambucil, cisplatin, irinotecan (CPT-11), SN-38, carboplatin, cladribine, cyclophosphamide, cytarabine, dacarbazine, docetaxel, dactinomycin, daunomycin glucuronide, daunorubicin, doxorubicin, 2-pyrrolinodoxorubicine (2P-DOX), cyano-morpholino doxorubicin, doxorubicin glucuronide, epirubicin glucuronide, estramustine, etoposide, etoposide glucuronide, etoposide phosphate, floxuridine (FUdR), 3′,5′-O-dioleoyl-FudR (FUdR-dO), fludarabine, flutamide, fluorouracil, gemcitabine, hydroxyurea, idarubicin, ifosfamide, L-asparaginase, leucovorin, lomustine, mechlorethamine, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, phenyl butyrate, procarbazine, paclitaxel, pentostatin, PSI-341, semustine, streptozocin, tamoxifen, taxanes, taxol, thalidomide, thioguanine, thiotepa, teniposide, topotecan, uracil mustard, velcade, vinblastine, vinorelbine, vincristine, or a combination thereof. 
     
     
         9 . The method of  claim 7 , wherein the anti-retroviral therapy comprises treatment with efavirenz, zidovudine, tenofovir, lamivudine, emtricitabine, didanosine, abacavir, stavudine, nevirapine, lopinavir, ritonavir, atazanavir, fosamprenavir, indinavir, nelfinavir, saquinavir, or a combination thereof. 
     
     
         10 . The method of  claim 1 , wherein the administration is oral, nasal, buccal, inhalational, rectal, vaginal, topical, orthotopic, intradermal, subcutaneous, intramuscular, intraperitoneal, intraarterial, intrathecal or intravenous. 
     
     
         11 . The method of  claim 1 , wherein exposure to the conjugated antibody is effective to reduce HIV infection or to limit the intercellular transmission of HIV to uninfected cells in vivo. 
     
     
         12 . The method of  claim 11 , wherein exposure to the conjugated antibody is effective to reduce HIV infection or to limit the intercellular transmission of HIV to uninfected cells in vivo without toxic side effects. 
     
     
         13 . The method of  claim 1 , wherein the cytotoxic drug binds to an intracellular molecule.