Radioimmunotherapy of interleukin-2Rα-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac

T. A. Waldmann, J. D. White, J. A. Carrasquillo, J. C. Reynolds, C. H. Paik, O. A. Gansow, M. W. Brechbiel, E. S. Jaffe, T. A. Fleisher, C. K. Goldman, L. E. Top, R. Bamford, S. Zaknoen, E. Roessler, Claude Sportes, R. England, H. Litou, J. A. Johnson, T. Jackson-White

Research output: Contribution to journalArticle

209 Scopus citations

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 doso-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 (≥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.

Original languageEnglish (US)
Pages (from-to)4063-4075
Number of pages13
JournalBlood
Volume86
Issue number11
DOIs
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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