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Antimicrobial Agents and Chemotherapy, February 1998, p. 383-388, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

TXU (Anti-CD7)-Pokeweed Antiviral Protein as a Potent Inhibitor of Human Immunodeficiency Virus

Fatih M. Uckun,1,2,* Lisa M. Chelstrom,2 Lisa Tuel-Ahlgren,2 Ilker Dibirdik,2 James D. Irvin,3 Mridula-Chandan Langlie,4 and Dorothea E. Myers4

Wayne Hughes Institute, St. Paul, Minnesota1; Biotherapy Program, University of Minnesota, Minneapolis, Minnesota2; Department of Chemistry, Southwest Texas State University, San Marcos, Texas3; and Alexander Parker Pharmaceuticals, Inc., Roseville, Minnesota4

Received 13 August 1997/Returned for modification 3 November 1997/Accepted 25 November 1997

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.

* Corresponding author. Mailing address: Wayne Hughes Institute, 2665 Long Lake Rd., St. Paul, MN 55113. Phone: (612) 697-9228. Fax: (612) 697-1042. E-mail: fatih_uckun{at}mercury.ih.org.

Antimicrobial Agents and Chemotherapy, February 1998, p. 383-388, Vol. 42, No. 2
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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