Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2).
Anti-Tac(Fv)-PE38 (LMB-2) is a recombinant, single-chain immunotoxin composed of the variable domains of the anti-Tac (anti-CD25) monoclonal antibody fused to a truncated form of Pseudomonas exotoxin (PE). Until now, this agent has been reported to be very cytotoxic toward T-cell but not B-cell leukemic cells freshly obtained from patients and is being tested clinically in patients with CD25+ malignancies of both B- and T-cell origin. Hairy cell leukemia (HCL) is a B-cell malignancy in which the cells are usually CD25+ and their ex vivo sensitivity to LMB-2 was unknown. Malignant cells from the first HCL patient to be tested were very sensitive to the cytotoxic effect of LMB-2 in vitro (IC50, 1.1 ng/ml), and this patient responded clinically to LMB-2 administered systemically. Therefore, we decided to assess the potential clinical utility of LMB-2 in other patients with HCL. We tested fresh leukemic cells from nine additional CD25+ HCL patients. LMB-2 was very cytotoxic ex vivo in all patients with IC50s as low as 0.5 ng/ml. Malignant cells freshly obtained from patients with chronic lymphocytic leukemia were also sensitive to LMB-2 but not as sensitive as cells from HCL patients. These results indicate that CD25+ HCL is a B-cell neoplasm that is particularly sensitive to LMB-2, and this agent may be useful in patients who have failed standard therapies.
Robbins
D H
DH
Laboratory of Clinical Pathology, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Margulies
I
I
Stetler-Stevenson
M
M
Kreitman
R J
RJ
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D005098:Exotoxins; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D000922:Immunotoxins / Q000633:toxicity*; D007943:Leukemia, Hairy Cell / Q000097:blood / Q000276:immunology / Q000473:pathology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000276:immunology / Q000473:pathology*; D015458:Leukemia, T-Cell / Q000097:blood / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C077707:B3(Fv)-PE38KDEL recombinant immunotoxin; D005098:Exotoxins; D000922:Immunotoxins