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

DAB389IL-2 is a recombinant fusion toxin composed of the diphtheria A chain and a portion 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-1α preceding exposure to DAB389IL-2 overcame their resistance to the toxin, IL-1α inducing high-affinity IL-2R expression. Similarly, pre-treatment with IL-1α 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-1α, suggesting a differential sensitivity which may be exploited clinically in the treatment of lymphomas.