       Document 0576
 DOCN  M9630576
 TI    Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell
       leukemia with Yttrium-90-labeled anti-Tac.
 DT    9603
 AU    Waldmann TA; White JD; Carrasquillo JA; Reynolds JC; Paik CH; Gansow OA;
       Brechbiel MW; Jaffe ES; Fleisher TA; Goldman CK; et al; Metabolism
       Branch, National Cancer Institute, National Institutes; of Health,
       Bethesda, MD 20892, USA.
 SO    Blood. 1995 Dec 1;86(11):4063-75. Unique Identifier : AIDSLINE
       MED/96082159
 AB    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.
 DE    Adult  Animal  Antibodies, Anti-Idiotypic/BIOSYNTHESIS  Antibodies,
       Monoclonal/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/  THERAPEUTIC USE
       Female  Human  Immunocompetence  Leukemia-Lymphoma, T-Cell, Acute,
       HTLV-I-Associated/IMMUNOLOGY/  METABOLISM/*RADIOTHERAPY  Lymphocyte
       Count  Male  Mice  Middle Age  *Radioimmunotherapy  Receptors,
       Interleukin-2/IMMUNOLOGY/METABOLISM  T-Lymphocytes  Yttrium
       Radioisotopes/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/  *THERAPEUTIC USE
       CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  CLINICAL TRIAL, PHASE II
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

