title: Treatment of human B-cell precursor leukemia in SCID mice using a combination of the investigational biotherapeutic agent B43-PAP with cytosine arabinoside.
abstract: Combined immunochemotherapy regimens using the investigational biotherapeutic agent B43(anti-CD19)-poke-weed antiviral protein (PAP) immunotoxin may offer an effective treatment for refractory B-cell precursor leukemias. The purpose of the present study was to explore and identify effective combinations of B43-PAP with standard chemotherapeutic drugs, including the anthracyclin doxorubicin, the epipodophyllotoxin etoposide, the nitrosurea carmustine, and the antimetabolite cytosine arabinoside. Here, we report that the B43-PAP plus cytosine arabinoside combination has potent antileukemic activity against human B-cell precursor leukemia in SCID mice and leads to 100% long-term event-free survival from an otherwise invariably fatal leukemia. Surprisingly, none of the other treatment protocols tested, including combinations of B43-PAP with carmustine, doxorubicin, or etoposide, proved more effective than B43-PAP alone.
authors.affiliation: Biotherapy Institute, Departments of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Messinger
authors.forename: Y
authors.initials: Y
authors.lastname: Yanishevski
authors.forename: V I
authors.initials: VI
authors.lastname: Avramis
authors.forename: O
authors.initials: O
authors.lastname: Ek
authors.forename: L M
authors.initials: LM
authors.lastname: Chelstrom
authors.forename: R
authors.initials: R
authors.lastname: Gunther
authors.forename: D E
authors.initials: DE
authors.lastname: Myers
authors.forename: J D
authors.initials: JD
authors.lastname: Irvin
authors.forename: W
authors.initials: W
authors.lastname: Evans
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000627:therapeutic use; D003561:Cytarabine / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D009368:Neoplasm Transplantation; D010940:Plant Proteins / Q000627:therapeutic use; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D054789:Ribosome Inactivating Proteins, Type 1; D013047:Specific Pathogen-Free Organisms; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D003561:Cytarabine; D005047:Etoposide; D004317:Doxorubicin; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein; D002330:Carmustine