Cancer Res. 1985 Sep;45(9 Suppl):4559s-4562s. Unique Identifier : AIDSLINE MED/85254470 Waldmann TA; Longo DL; Leonard WJ; Depper JM; Thompson CB; Kronke M; Goldman CK; Sharrow S; Bongiovanni K; Greene WC
Abstract:
Interleukin-2 (IL-2) is a lymphokine synthesized by some T-cells following activation. Resting T-cells do not express IL-2 receptors, but receptors are rapidly expressed on T-cells following interaction of antigens, mitogens, or monoclonal antibodies with the antigen-specific T-cell receptor complex. Using anti-Tac, a monoclonal antibody that recognizes the IL-2 receptor, the receptor has been purified and shown to be a Mr 33,000 peptide that is posttranslationally glycosylated to a Mr 55,000 mature form. Normal resting T-cells and most leukemic T-cell populations do not express IL-2 receptors; however, the leukemic cells of the 11 patients examined who had human T-cell lymphotropic virus-associated adult T-cell leukemia expressed the Tac antigen. In human T-cell lymphotropic virus-I infected cells, the Mr 42,000 long open reading frame protein encoded in part by the pX region of this virus may act as a transacting transcriptional activator that induces IL-2 receptor gene transcription, thus providing an explanation for the constant association of IL-2 receptor expression with adult T-cell lymphotropic virus-I infection of lymphoid cells. The constant expression of large numbers of IL-2 receptors which may be aberrant may play a role in the uncontrolled growth of adult T-cell leukemia cells. Two patients with Tac-positive adult T-cell leukemia have been treated with the anti-Tac. One of the patients had 6- and 3-mo remissions of his leukemia following two courses of therapy with this monoclonal antibody directed toward this growth factor receptor.
Keywords: Adult Antibodies, Monoclonal/THERAPEUTIC USE Cell Line Genes, Viral Human *HTLV-BLV Viruses/GENETICS Leukemia/BLOOD/*MICROBIOLOGY/THERAPY Lymphocyte Transformation Male Receptors, Immunologic/ANALYSIS/*BIOSYNTHESIS/IMMUNOLOGY/ ISOLATION & PURIF Retroviridae Infections/BLOOD/MICROBIOLOGY T-Lymphocytes/*METABOLISM/MICROBIOLOGY Transcription Factors Transcription, Genetic Viral Proteins/GENETICS/PHYSIOLOGY JOURNAL ARTICLE
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