Open AccessTXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus
Author(s) -
Fatih M. Uckun,
Lisa M. Chelstrom,
L Tuel-Ahlgren,
İlker Dıbırdık,
James D. Irvin,
M C Langlie,
Dorothea E. Myers
Publication year - 1998
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.42.2.383
Subject(s) - immunoconjugate , zidovudine , in vitro , virology , medicine , virus , immunology , biology , antibody , viral disease , monoclonal antibody , biochemistry
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.
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