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PubMed · 16997177

BL22 and lymphoid malignancies.

Robert J Kreitman·Ira Pastan
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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.

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AntibodiesClinical Trials, Phase I as TopicClinical Trials, Phase II as TopicEnterotoxinsHumansLeukemia, Hairy CellLeukemia, Lymphocytic, Chronic, B-CellModels, ImmunologicalPrecursor Cell Lymphoblastic Leukemia-LymphomaJournal ArticleResearch Support, N.I.H., IntramuralReview

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Robert J Kreitman, Ira Pastan. 2006. BL22 and lymphoid malignancies.. https://doi.org/10.1016/j.beha.2006.06.009

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