BL22 and lymphoid malignancies.

Abstract

BL22 is a recombinant immunotoxin containing a truncated form of the bacterial toxin Pseudomonas exotoxin A attached to an Fv fragment of an anti-CD22 monoclonal antibody. Its mechanism of action involves binding to CD22, being internalized into the target cell by endocytosis, being processed to generate a free toxin fragment which is translocated into the cytoplasm, and finally induction of cell death by catalytic inactivation of elongation factor 2. In phase-I testing BL22 was very active in chemoresistant hairy-cell leukemia (HCL), with 19 (61%) of 31 patients achieving complete remission (CR). The low blood counts (cytopenias) which are characteristic of HCL improved in all complete and partial responders. Dose-limiting toxicity in HCL was due to a reversible hemolytic uremic syndrome (HUS), observed only during cycles 2 or 3. Already under way are a phase-II trial in HCL and phase-I trials in chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia (ALL) administering BL22 in a modified protocol in an effort to prevent HUS.

• Authors: Robert J Kreitman, Ira Pastan
• Journal: Best practice & research. Clinical haematology (Best Pract Res Clin Haematol) Vol. 19 Issue 4 Pg. 685-99 ( 2006) ISSN: 1521-6926 [Print] Netherlands
• PMID: 16997177 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Review)

Chemical References

• Antibodies
• Enterotoxins
• RFB4(dsFv)-PE38 recombinant immunotoxin

Topics

• Antibodies (administration & dosage, adverse effects, therapeutic use)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Enterotoxins (administration & dosage, adverse effects, therapeutic use)
• Humans
• Leukemia, Hairy Cell (drug therapy, immunology)
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy, immunology)
• Models, Immunological
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, immunology)