Lymphokine receptors: a target for immunotherapy of lymphomas (Meeting abstract).

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

Lymphokine receptors: a target for immunotherapy of lymphomas (Meeting abstract).

Fifth International Conference on Malignant Lymphoma, June 9-12, 1993, Lugano, Switzerland, p. 46, 1993.. Unique Identifier : AIDSLINE ICDB/95606931
Waldmann TA; NCI, Bethesda, MD 20892

Abstract: Many lymphomas express lymphokine receptors not expressed by normal resting cells. Such receptors provide rational targets for immunotherapy. Specifically, the leukemic cells of patients with human T-cell leukemia virus I (HTLV-I)-associated ATL express the IL-2 receptor alpha, beta and gamma subunits. In contrast, normal resting cells do not express the IL-2 receptor alpha-subunit identified by the anti-Tac monoclonal antibody. Patients with ATL were treated with different forms of IL-2 receptor-directed therapy to exploit the difference in IL-2 receptor expression between normal and malignant cells. Using the unmodified anti-Tac monoclonal antibody, seven of the 19 patients with ATL treated have undergone a remission, in two cases complete. There was no toxicity observed. 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 complementary-determining regions from the mouse antibody with the remainder of the antibody derived from human IgG1-kappa. This antibody is dramatically less immunogenic than the murine version, has improved pharmacokinetics 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- or beta-emitting radionuclides. In a clinical trial with 90Y-anti-Tac at the doses used (5, 10 and 15 mCi), 11 of the 17 patients with ATL treated underwent a partial of sustained complete remission. Thus, the clinical application of IL-2 receptor-directed therapy represents a new perspective for the treatment of certain lymphomas including HTLV-I-associated ATL.

Keywords: Antibodies, Monoclonal/THERAPEUTIC USE Human Lymphoma, AIDS-Related/METABOLISM/*THERAPY *Radioimmunotherapy Receptors, Interleukin-2/*METABOLISM Yttrium Radioisotopes/THERAPEUTIC USE ABSTRACT
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