Treatment of human B-cell precursor leukemia in SCID mice using a combination of the investigational biotherapeutic agent B43-PAP with cytosine arabinoside.
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.
Messinger
Y
Y
Biotherapy Institute, Departments of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Yanishevski
Y
Y
Avramis
V I
VI
Ek
O
O
Chelstrom
L M
LM
Gunther
R
R
Myers
D E
DE
Irvin
J D
JD
Evans
W
W
Uckun
F M
FM
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
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