Inhibition of HIV-1 replication in seropositive patients' CD4+ T-cells by pokeweed antiviral protein-monoclonal antibody conjugates.
Pokeweed antiviral protein (PAP) inhibits HIV-1 replication in HIV-1 infected CD4+ cells and PAP targeted to CD4+T-cells by conjugation with monoclonal antibodies (mAb) against CD4 is approximately 1000 times more potent than non-conjugated PAP. Furthermore, PAP-antiCD4 inhibits HIV-1 production in seropositive patients' CD4+ T-cells activated with mAb to CD3 which was found to be the most potent means to activate HIV-1 production. These findings, together with previous observations that PAP-mAb conjugates have an in vivo plasma half-life of about 30 times that of non-conjugated PAP, suggest that PAP-antiCD4 may be a useful therapy in HIV-infected humans. Additionally, because PAP is known to have antiviral activity against several other human viruses, PAP-mAb conjugates may also have clinical potential for treating other viral diseases.
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
J M
JM
Zarling
P A
PA
Moran
O
O
Haffar
M
M
Diegel
D E
DE
Myers
V
V
Kuelbeck
J A
JA
Ledbetter
F M
FM
Uckun
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D006679:HIV Seropositivity / Q000628:therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1; D014779:Virus Replication / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein