In vivo toxicity, pharmacokinetics, and antileukemic activity of TXU (anti-CD7)-pokeweed antiviral protein immunotoxin

Barbara Waurzyniak, Elizabeth A. Schneider, Nilgun Tumer, Yuri Yanishevski, Roland Gunther, Lisa M. Chelstrom, Heather Wendorf, Dorothea E. Myers, James D. Irvin, Yoav Messinger, Onur Ek, Tamer Zeren, Mridula Chandan Langlie, William E. Evans, Fatih M. Uckun

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

We evaluated the TXU (anti-CD7) pokeweed antiviral protein (PAP) immunotoxin in both murine and nonhuman primate models. TXU-PAP caused dose-limiting cardiac toxicity in BALB/c mice. In a SCID mouse model of invariably fatal human T-lineage acute lymphoblastic leukemia (ALL), TXU-PAP therapy resulted in a marked improvement of leukemia-free survival without any side effects. Whereas 100% of control mice treated with PBS, unconjugated TXU antibody, or B43-PAP (an immunotoxin that does not react with T-lineage ALL cells) died of disseminated human leukemia within 80 days (median survival, 37 days), 80 ± 13% of SCID mice treated with 15 μg of TXU-PAP (median survival, > 120 days) and 100% of mice treated with 30 μg of TXU-PAP (median survival, > 120 days) remained alive and free of leukemia for > 120 days. In cynomolgus monkeys, TXU-PAP showed favorable pharmacokinetics with an elimination half-life of 8.1-8.7 h. The monkeys treated with TXU-PAP at dose levels of 0.05 mg/kg/day x 5 days and 0.10 mg/kg/day x 5 days tolerated the therapy very well, without any significant clinical compromise or side effects, and at necropsy, no gross or microscopic lesions were found. This study provides a basis for further evaluation of TXU-PAP as an investigational biotherapeutic agent in the treatment of T-lineage ALL.

Original languageEnglish (US)
Pages (from-to)881-890
Number of pages10
JournalClinical Cancer Research
Volume3
Issue number6
StatePublished - Jun 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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