In Vitro and In Vivo Antileukemic Activity of B43-Pokeweed Antiviral Protein Against Radiation-Resistant Human B-Cell Precursor Leukemia Cells

Abstract

B-cell precursor (BCP) leukemia is the most common form of childhood cancer and represents one of the most radiation-resistant forms of human malignancy. In this study, we examined the antileukemic efficacy of the B43 (anti-CD19)-pokeweed antiviral protein (B43-PAP) immunotoxin against radiation-resistant BCP leukemia cells. B43-PAP caused apoptosis of radiation-resistant primary BCP leukemia cells, killed greater than 99% of radiation-resistant primary leukemic progenitor cells from BCP leukemia patients, and conferred extended survival to severe combined immunodeficiency (SCID) mice xenografted with radiation-resistant human BCP leukemia. Furthermore, the combination of B43-PAP and total body irradiation (TBI) was more effective than TBI alone in two SCID mouse bone marrow transplantation models of radiation-resistant human BCP leukemia. Thus, B43-PAP may prove useful in the treatment of radiation-resistant BCP leukemia.