Lymphokine receptors: a target for immunotherapy of lymphomas.
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.
Waldmann
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Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D015368:Human T-lymphotropic virus 1 / Q000302:isolation & purification; D006801:Humans; D007167:Immunotherapy; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000628:therapy; D008223:Lymphoma / Q000737:chemistry / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D015375:Receptors, Interleukin-2