Immunotoxins in the treatment of refractory hairy cell leukemia.
An increasing number of patients who have hairy cell leukemia (HCL) have persistent disease that requires treatment, despite purine analogs, splenectomy, interferon, and rituximab. Many of these patients have been treated successfully with immunotoxins. An immunotoxin contains a protein toxin connected to a cell-binding ligand, such as an antibody. An immunotoxin recognizes the target cell, internalizes, and the toxin translocates to the cytosol where it inhibits protein synthesis enzymatically. Immunotoxins that show activity in HCL contain truncated Psedomonas exotoxin fused to the Fv fragments of anti-CD25 or anti-CD22 monoclonal antibodies. Both agents, termed LMB-2 and BL22, respectively, have been tested in patients who have HCL after failure of purine analogs and other therapies; major responses have been achieved in most patients.
Kreitman
Robert J
RJ
Clinical Immunotherapy Section, Laboratory of Molecular Biology, Center 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
D036002:ADP Ribose Transferases / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000276:immunology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005098:Exotoxins / Q000276:immunology / Q000627:therapeutic use*; D007135:Immunoglobulin Variable Region / Q000276:immunology / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012074:Remission Induction / Q000379:methods; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology / Q000627:therapeutic use*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D005098:Exotoxins; D007135:Immunoglobulin Variable Region; D000922:Immunotoxins; D015375:Receptors, Interleukin-2; D051918:Sialic Acid Binding Ig-like Lectin 2; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C077707:B3(Fv)-PE38KDEL recombinant immunotoxin