Selective killing of HIV-infected cells by anti-gp120 immunotoxins.
Either ricin A chain (RAC) or Pseudomonas exotoxin (PE) was conjugated with a murine monoclonal antibody (0.5 beta) directed against an external envelope glycoprotein (gp120) of human immunodeficiency virus (HIV). Effects of the immunotoxins produced against infected cells were evaluated. Selective inhibition of the proliferation and killing of chronically HIV infected cells were observed in the presence of the immunotoxins. To determine the feasibility of the immunotoxins against the infected cells in seropositive subjects, we attempted to detect gp120-bearing cells in peripheral blood mononuclear cells (PBM) by cytofluorography. Cells in the monocyte/macrophage region of 2 of 10 PBM samples from HIV-infected individuals were found to react with 0.5 beta (18.1% and 12.8%). Furthermore, the cell population which was reactive with 0.5 beta was also susceptible to RAC conjugated with 0.5 beta. These results suggest that the strategy of using anti-gp120 immunotoxin to eliminate HIV-infected cells may be feasible in infected individuals.
Matsushita
S
S
Blood Transfusion Service, Kumamoto University Medical School, Japan.
Koito
A
A
Maeda
Y
Y
Hattori
T
T
Takatsuki
K
K
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D008969:Molecular Sequence Data; D011549:Pseudomonas / Q000378:metabolism; D012276:Ricin
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D015699:HIV Envelope Protein gp120; D000922:Immunotoxins; D012276:Ricin