An anti-CD72 immunotoxin against therapy-refractory B-lineage acute lymphoblastic leukemia.

Abstract

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)

• Authors: D E Myers, F M Uckun
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 18 Issue 1-2 Pg. 119-22 (Jun 1995) ISSN: 1042-8194 [Print] United States
• PMID: 8580813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Differentiation, B-Lymphocyte
• Antineoplastic Agents, Phytogenic
• CD72 protein, human
• Immunotoxins
• Plant Proteins
• Ribosome Inactivating Proteins, Type 1
• N-Glycosyl Hydrolases
• pokeweed antiviral protein

Topics

• Animals
• Antibodies, Monoclonal (chemistry, immunology, pharmacology)
• Antigens, CD (chemistry, immunology, pharmacology)
• Antigens, Differentiation, B-Lymphocyte (chemistry, immunology, pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Burkitt Lymphoma (drug therapy)
• Humans
• Immunotoxins (chemistry, pharmacology)
• Leukemia, Lymphoid (drug therapy)
• Mice
• Mice, SCID
• N-Glycosyl Hydrolases
• Plant Proteins (pharmacology)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Ribosome Inactivating Proteins, Type 1