Treatment of HIV tissue culture infection with monoclonal antibody-ricin A chain conjugates.
mAb 907 is directed against the envelope protein of the HIV. The epitope recognized by this antibody is expressed in moderate density on the surface of tissue culture cells infected with the LAV/HTLV-IIIB strain of HIV. We have coupled antibody 907 to ricin A chain (RAC). The antibody-RAC conjugate inhibited protein synthesis and cell growth in HIV-infected cells. An irrelevant antibody conjugated to RAC had no effect. Most important, treatment of infected cells with the conjugate markedly inhibited the production of infectious virus, as measured by the production of viral foci on susceptible monolayer cells. Exposure of HIV-infected target cells to the conjugate for as short a period as 1 h resulted in cell death. Serum of AIDS patients inhibited, but did not completely suppress, the toxicity of the 907-RAC conjugate. A second antibody, designated BM-1, which recognizes a carbohydrate Ag on the surface of virally infected cells, was conjugated to RAC. The BM-1-RAC conjugate did not kill HIV-infected cells, highlighting the importance of the target Ag. Immunotoxins produced with antibodies that recognize Ag on the surface of HIV-infected cells may have utility in the therapy of AIDS.
Pincus
S H
SH
Laboratory of Microbial Structure and Function, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840.
Wehrly
K
K
Chesebro
B
B
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000382:microbiology; D000208:Acute Disease; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D001667:Binding, Competitive; D002460:Cell Line; D002470:Cell Survival; D046508:Culture Techniques; D004306:Dose-Response Relationship, Immunologic; D006678:HIV / Q000032:analysis / Q000276:immunology* / Q000502:physiology; D015699:HIV Envelope Protein gp120; D006801:Humans; D000922:Immunotoxins / Q000633:toxicity*; D007700:Kinetics; D007983:Lewis Blood Group Antigens / Q000276:immunology; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D012191:Retroviridae Proteins / Q000032:analysis; D012276:Ricin / Q000633:toxicity*; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D000922:Immunotoxins; D007983:Lewis Blood Group Antigens; D011500:Protein Synthesis Inhibitors; D012191:Retroviridae Proteins; D012276:Ricin