TXU (anti-CD7)-pokeweed antiviral protein as a potent inhibitor of human immunodeficiency virus.
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.
Uckun
F M
FM
Wayne Hughes Institute, St. Paul, Minnesota 55113, USA. faith_uckun@mercury.ih.org
Chelstrom
L M
LM
Tuel-Ahlgren
L
L
Dibirdik
I
I
Irvin
J D
JD
Langlie
M C
MC
Myers
D E
DE
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
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