Best Practice & Research Clinical Haematology
Volume 19, Issue 4 , Pages 685-699, December 2006

BL22 and lymphoid malignancies

  • Robert J. Kreitman, MD (Chief, Clinical Immunotherapy Section, Laboratory of Molecular Biology)

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1 301 496 6947; Fax: +1 301 576 3920.
  • Ira Pastan, MD (Chief, Laboratory of Molecular Biology)

Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA

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.

Key words: toxin, leukemia, lymphoma, Fv, Pseudomonas exotoxin, CD22, CD25, monoclonal antibody, leukemia, hairy cell, purine analog

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PII: S1521-6926(06)00045-4

doi:10.1016/j.beha.2006.06.009

Best Practice & Research Clinical Haematology
Volume 19, Issue 4 , Pages 685-699, December 2006

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