In vitro and in vivo antileukemic activity of B43-pokeweed antiviral protein against radiation-resistant human B-cell precursor leukemia cells.

the most common form of childhood cancer and represents one of the most radiation- resistant forms of human malignancy. In this study, we ex- amined the antileukemic efficacy of the B43 (anti-CD19)- pokeweed antiviral protein (B43-PAPI immunotoxin against radiation-resistant BCP leukemia cells. B43-PAP caused apoptosis of radiation-resistant primary BCP leukemia cells, killed greater than 999'0 of radiation-resistant primary leuke- mic progenitor cells from BCP leukemia patients, and con- -CELL PRECURSOR (BCP) leukemia is the most com- mon form of childhood cancer"6 and represents one of the most radiation-resistant forms of human malignancy."" Recent studies demonstrated that greater than 75% of clono- genic BCP leukemia cells from more than one third of the patients with newly diagnosed disease, and virtually all of the relapsed patients, are able to repair potentially lethal or sublethal DNA damage induced by radiation doses that correspond to the clinical total body irradiation (TBI) dose fractions (ie, 2 to 3 Gy)."" Consequently, the vast majority of high-risk BCP leukemia patients undergoing TB1 in the context of bone marrow transplantation (BMT) relapse within the first 12 months, and only 15% to 20% survive disease-free beyond the first 2 year^.^.".'^ Thus, the major challenge in BMT for BCP acute lymphoblastic leukemia (ALL) is the development of novel and more effective condi- tioning strategies. Here, we provide experimental evidence that B43-poke- weed antiviral protein (PAP), a potent anti-CD19 immuno- toxin, causes apoptosis of radiation-resistant primary BCP leukemia cells, kills greater than 99% of radiation-resistant leukemic progenitor cells from patients with leukemia, and confers extended survival to severe combined immunodefi- B