Immunobiological treatments of hairy-cell leukaemia.
Hairy cell leukaemia (HCL) is extremely responsive to purine analogue theropy developed during the early 1990s, but some patients have emerged with resistance to purine analogues. For these patients, as well as for those with primarily refractory HCL, new treatments are necessary. Several new therapeutic options have been developed for the salvage treatment of HCL. These include recombinant immunotoxins and unlabelled monoclonal antibodies (mAbs). Recombinant immunotoxins are chimeric proteins in which the Fv portion of a mAb is fused to a 38 kDa fragment of Pseudomonas exotoxin A. Two recombinant immunotoxins, BL22 and LMB-2, targeting CD22 and CD25, respectively, have demonstrated efficacy in patients with HCL resistant to purine analogues. BL22 was reported to induce complete remissions (CRs) in the majority of patients with cladribine-resistant HCL; its clinical efficacy and safety profile are currently being further defined. The unlabelled mAb rituximab has also been reported to induce responses in the majority of HCL patients treated, and several CRs have been observed.
Kreitman
Robert J
RJ
Laboratory of Molecular Biology, Centers for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 5106, Bethesda, MD 20892-4255, USA. kreitmar@mail.nih.gov
Pastan
Ira
I
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017338:Cladribine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005098:Exotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D000922:Immunotoxins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D012074:Remission Induction / Q000379:methods; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C077707:B3(Fv)-PE38KDEL recombinant immunotoxin; D005098:Exotoxins; D000922:Immunotoxins; D017338:Cladribine