An anti-CD72 immunotoxin against therapy-refractory B-lineage acute lymphoblastic leukemia.
CD72 is a broadly expressed B-lineage specific surface antigen. We used J3-109(anti-CD72) monoclonal antibody to examine primary neoplastic cells from patients with acute leukemia for CD72 expression. CD72 was present at high levels in 70 of 100 B-lineage acute lymphoblastic leukemias (ALL), but it was not expressed on cells from 23 T-lineage ALL patients or 9 acute myeloblastic leukemia patients. We have prepared an anti-CD72 immunotoxin by conjugating J3-109 monoclonal antibody to the ribosome-inactivating protein, PAP.J3-109-PAP effectively killed > 99.9% of clonogenic blasts from a CD72+ B-lineage ALL cell line. We used a SCID mouse model of aggressive human pre-B ALL to evaluate the in vivo anti-leukemic efficacy of the J3-109-PAP immunotoxin. An intravenous challenge with 1 x 10(6) NALM-6-UM-1(pre-B ALL) cells caused 100% of SCID mice to die of disseminated leukemia within 41 days. Importantly, a three-day treatment with non-toxic doses of J3-109-PAP significantly improved event-free survival of SCID mice. The Kaplan-Meier estimate (+/- standard error) of the probability of event-free survival at 2 months after inoculation of NALM-6-UM-1 cells was 40 +/- 16% for SCID mice treated with a total of 15 micrograms J3-109-PAP (median survival = 58 days) as compared to 0 +/- 0% for PBS treated mice (median survival = 34 days). At 6 months after the inoculation of NALM-6-UM-1 cells, 10 +/- 9% of the J3-109-PAP treated SCID mice were still alive with no evidence of leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Myers
D E
DE
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis 55113, USA.
Uckun
F M
FM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000188:drug therapy*; D006801:Humans; D000922:Immunotoxins / Q000737:chemistry / Q000494:pharmacology*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D051379:Mice; D016513:Mice, SCID; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D054789:Ribosome Inactivating Proteins, Type 1
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000972:Antineoplastic Agents, Phytogenic; C064228:CD72 protein, human; D000922:Immunotoxins; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein