Document 0360
 DOCN  M9460360
 TI    Lymphokine receptors: a target for immunotherapy of lymphomas.
 DT    9408
 AU    Waldmann TA; Metabolism Branch, National Cancer Institute, National
       Institutes; of Health, Bethesda, Maryland.
 SO    Ann Oncol. 1994;5 Suppl 1:S13-7. Unique Identifier : AIDSLINE
       MED/94226936
 AB    Lymphoma cells often express lymphokine receptors that provide a target
       for therapy. For example, malignant cells of patients with
       HTLV-1-associated adult T-cell leukemia/lymphoma (ATL) express IL-2
       receptors. In contrast, normal resting cells do not express the IL-2
       receptors identified by the anti-Tac monoclonal antibody. Using the
       unmodified anti-Tac monoclonal antibody, one-third of the 19 patients
       treated with ATL have undergone a remission. However, unmodified murine
       monoclonal antibodies are limited by their immunogenicity and their poor
       effector functions. To address these issues, we used genetic engineering
       to produce humanized anti-Tac that contains the
       complementarity-determining regions from the mouse with the remainder of
       the antibody derived from human IgG1-kappa. Humanized anti-Tac is
       dramatically less immunogenic than the murine versions and, in contrast
       to the parent antibody, manifests antibody-dependent cellular
       cytotoxicity with human mononuclear cells. To enhance its effector
       function, anti-Tac was armed with toxins or with alpha- and
       beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac, 11
       of the 17 patients with ATL underwent a partial or sustained complete
       remission. Thus, the clinical application of
       lymphokine-receptor-directed therapy provides a new perspective for
       treatment of certain lymphomas, including HTLV-1-associated ATL.
 DE    Antibodies, Monoclonal/ADMINISTRATION & DOSAGE  Antineoplastic
       Agents/ADMINISTRATION & DOSAGE  Human  HTLV-I/ISOLATION & PURIF
       *Immunotherapy  Leukemia, T-Cell, Acute/THERAPY
       Lymphoma/CHEMISTRY/*THERAPY  *Receptors, Interleukin-2/ANALYSIS
       Structure-Activity Relationship  JOURNAL ARTICLE  REVIEW  REVIEW,
       TUTORIAL

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