IN-VITRO AND IN-VIVO ANTILEUKEMIC ACTIVITY OF B43-POKEWEED ANTIVIRAL PROTEIN AGAINST RADIATION-RESISTANT HUMAN B-CELL PRECURSOR LEUKEMIA-CELLS

B-cell precursor (BCP) leukemia is the most common form of childhood c ancer and represents one of the most radiation-resistant forms of huma n malignancy. In this study, we examined the antileukemic efficacy of the B43 (anti-CD19)-pokeweed antiviral protein (B43-PAP) immunotoxin a gainst radiation-resistant BCP leukemia cells. B43-PAP caused apoptosi s of radiation-resistant primary BCP leukemia cells, killed greater th an 99% of radiation-resistant primary leukemic progenitor cells from B CP leukemia patients, and conferred extended survival to severe combin ed immunodeficiency (SCID) mice xenografted with radiation-resistant h uman BCP leukemia. Furthermore, the combination of B43-PAP and total b ody irradiation (TBI) was more effective than TBI alone in two SCID mo use bone marrow transplantation models of radiation-resistant human BC P leukemia. Thus, B43-PAP may prove useful in the treatment of radiati on-resistant BCP leukemia. (C) 1995 by The American Society of Hematol ogy.