IN-VIVO TOXICITY, PHARMACOKINETICS, AND ANTILEUKEMIC ACTIVITY OF TXU (ANTI-CD7)-POKEWEED ANTIVIRAL PROTEIN IMMUNOTOXIN

We evaluated the TXU (anti-CD7)-pokeweed antiviral protein (PAP) immun otoxin in both murine and nonhuman primate models, TXU-PAP caused dose -limiting cardiac toxicity in BALB/c mice, In a SCID mouse model of in variably fatal human T-lineage acute lymphoblastic leukemia (ALL), TXU -PAP therapy resulted in a marked improvement of leukemia-free surviva l without any side effects, Whereas 100% of control mice treated with PBS, unconjugated TXU antibody, or B43-PAP (an immunotoxin that does n ot react with T-lineage ALL cells) died of disseminated human leukemia within 80 days (median survival, 37 days), 80 +/- 13% of SCID mice tr eated with 15 mu g of TXU-PAP (median survival, >120 days) and 100% of mice treated with 30 mu g of TXU-PAP (median survival, >120 days) rem ained alive and free of leukemia for >120 days, In cynomolgus monkeys, TXU-PAP showed favorable pharmacokinetics with an elimination half-li fe 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 therap y very well, without any significant clinical compromise or side effec ts, and at necropsy, no gross or microscopic lesions were found, This study provides a basis for further evaluation of TXU-PAP as an investi gational biotherapeutic agent in the treatment of T-lineage ALL.