title: Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac.
abstract: Adult T-cell leukemia (ATL) is a malignancy of mature lymphocytes caused by the retrovirus human T-cell lymphotropic virus-I. It is an aggressive leukemia with a median survival time of 9 months; no chemotherapy regimen appears successful in inducing long-term disease-free survival. The scientific basis of the present study is that ATL cells express high-affinity interleukin-2 receptors identified by the anti-Tac monoclonal antibody, whereas normal resting cells do not. To exploit this difference, we administered anti-Tac armed with Yttrium-90 (90Y) to 18 patients with ATL initially (first 9 patients) in a phase I dose-escalation trial and subsequently (second group of 9 patients) in a phase II trial involving a uniform 10-mCi dose of 90Y-labeled anti-Tac. Patients undergoing a remission were permitted to receive up to eight additional doses. At the 5- to 15-mCi doses used, 9 of 16 evaluable patients responded to 90Y anti-Tac with a partial (7 patients) or complete (2 patients) remission. The responses observed represent improved efficacy in terms of length of remission when compared with previous results with unmodified anti-Tac. Clinically meaningful (> or = grade 3) toxicity was largely limited to the hematopoietic system. In conclusion, radioimmunotherapy with 90Y anti-Tac directed toward the IL-2R expressed on ATL cells may provide a useful approach for treatment of this aggressive malignancy.
mesh_terms: D000328:Adult; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007121:Immunocompetence; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008875:Middle Aged; D016499:Radioimmunotherapy; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes; D015021:Yttrium Radioisotopes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015375:Receptors, Interleukin-2; D015021:Yttrium Radioisotopes