BL22 and lymphoid malignancies.
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.
Kreitman
Robert J
RJ
Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5124b, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov
Pastan
Ira
I
D000906:Antibodies / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004768:Enterotoxins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D018448:Models, Immunological; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology
D000906:Antibodies; D004768:Enterotoxins; C431326:RFB4(dsFv)-PE38 recombinant immunotoxin