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

Dominique Salard, Timothy M. Kuzel, Ellen Samuelson, Steven Rosen, Ouahid Bakouche*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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, pretreatment 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.

Original languageEnglish (US)
Pages (from-to)223-234
Number of pages12
JournalJournal of Clinical Immunology
Volume18
Issue number3
DOIs
StatePublished - Jun 17 1998

Keywords

  • Cytotoxicity
  • IL-2-diphtheria toxin fusion protein
  • Interleukin-1α (IL-1α)
  • Neoplastic lymphocytes
  • Sezary syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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