Interleukin-1α increases the preferential cytotoxicity of an interleukin-2-diphtheria toxin fusion protein against neoplastic lymphocytes from patients with the Sezary syndrome compared to normal lymphocytes

• Published in: Journal of clinical immunology Vol. 18; no. 3; pp. 223 - 234
• Main Authors: SALARD, D, KUZEL, T. M, SAMUELSON, E, ROSEN, S, BAKOUCHE, O
• Format: Journal Article
• Language: English
• Published: New York, NY Kluwer/Plenum 01.05.1998; Springer Nature B.V
• Subjects: Affinity; Biological and medical sciences; Cell Line; Cytotoxicity; Diphtheria; Diphtheria toxin; Diphtheria Toxin - pharmacology; Drug Synergism; Fusion protein; Hematologic and hematopoietic diseases; Humans; Interleukin 2; Interleukin 2 receptors; Interleukin-1 - pharmacology; Interleukin-2 - pharmacology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes; Lymphocytes - drug effects; Lymphocytes T; Medical sciences; Monocytes; Mycosis; Mycosis fungoides; Mycosis Fungoides - blood; Mycosis Fungoides - drug therapy; Patients; Receptors, Interleukin-2 - drug effects; Receptors, Interleukin-2 - metabolism; Recombinant Fusion Proteins - pharmacology; Sezary syndrome; Sezary Syndrome - blood; Sezary Syndrome - drug therapy; T-cell lymphoma; T-Lymphocytes - drug effects; Human; Cell culture; Skin disease; Cytokine; Interleukin 1α; Cytotoxicity; Malignant hemopathy; Non Hodgkin lymphoma; Diphtheria; Peripheral T cell lymphoma; Biological activity; Infection; Toxin; Chronic; Cutaneous hematologic disease; Interleukin 2; Sezary syndrome; Lymphoproliferative syndrome; Bacteriosis; Recombinant protein; Molecular biology; Fusion protein; Lymphocyte; Comparative study
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1023/A:1020587123523

DAB389IL-2 is a recombinant fusion toxin composed of the diphtheria A chain and a protion of the translocating region of the diphtheria B chain, replacing the receptor binding domain with human IL-2. DAB389IL-2 can be safely administered to humans with mycosis fungoides (MF) or Sezary syndrome (SS), and antineoplastic effects occur. This agent binds optimally to the high-affinity IL-2R. The decreased efficiency of uptake by neoplastic cells which do not express the high-affinity IL-2R represents a potential limitation. Treatment of the HUT-78 cutaneous T-cell lymphoma with IL-1 alpha preceding exposure to DAB389IL-2 overcame their resistance to the toxin, IL-1 alpha inducing high-affinity IL-2R expression. Similarly, pretreatment with IL-1 alpha of SS patient lymphocytes demonstrated increased cytotoxicity compared to treatment with the fusion toxin alone. Normal lymphocytes and monocytes were not sensitive to DAB389IL-2 when pretreated with IL-1 alpha, suggesting a differential sensitivity which may be exploited clinically in the treatment of lymphomas.