title: TXU (anti-CD7)-pokeweed antiviral protein as a potent inhibitor of human immunodeficiency virus.
abstract: We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, as well as in a surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model of human AIDS. The present report documents in a side-by-side comparison the superior in vitro anti-HIV-1 activity of TXU-PAP compared to the activities of zidovudine, 2',3'-didehydro-2',3'-dideoxythymidine, unconjugated PAP, and B53-PAP, an anti-CD4-PAP immunoconjugate. Notably, TXU-PAP elicited potent anti-HIV activity in the Hu-PBL-SCID mouse model of human AIDS without any side effects and at doses that were very well tolerated by cynomolgus monkeys. Furthermore, plasma samples from TXU-PAP-treated cynomolgus monkeys showed potent anti-HIV-1 activity in vitro.
authors.affiliation: Wayne Hughes Institute, St. Paul, Minnesota 55113, USA. faith_uckun@mercury.ih.org
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
authors.forename: L M
authors.initials: LM
authors.lastname: Chelstrom
authors.forename: L
authors.initials: L
authors.lastname: Tuel-Ahlgren
authors.forename: I
authors.initials: I
authors.lastname: Dibirdik
authors.forename: J D
authors.initials: JD
authors.lastname: Irvin
authors.forename: M C
authors.initials: MC
authors.lastname: Langlie
authors.forename: D E
authors.initials: DE
authors.lastname: Myers
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology* / Q000627:therapeutic use*; D008252:Macaca fascicularis; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1; D018119:Stavudine / Q000627:therapeutic use; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D018796:Immunoconjugates; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C111079:TXU-pokeweed antiviral protein, Phytolacca; D015215:Zidovudine; D018119:Stavudine; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein