Adult T cell leukemia: A potential target for ricin A chain immunotoxins

M. Kronke, J. M. Depper, W. J. Leonard, E. S. Vitetta, T. A. Waldmann, W. C. Greene

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Adult T cell leukemia (ATL) is an almost uniformly fatal malignancy of mature T cells associated with human T cell leukemia/lymphoma virus type 1 (HTLV-1) infection. Cells from this leukemia are characterized by the expression of large numbers of receptors for interleukin 2 (IL-2). In an attempt to prepare an immunotoxin with selective cytotoxicity for ATL cells, we conjugated anti-Tac, a monoclonal anti-IL-2 receptor antibody, to purified ricin A chains. Although unmodified anti-Tac had no effect on the protein synthesis of these cells, anti-Tac-ricin A chain conjugates produced half-maximal inhibition of protein synthesis in HTLV-1-infected leukemic T cell lines at concentrations of 2 to 6 x 10-10 mol/L (ID50). An essentially identical ID50 was obtained with leukemic peripheral blood T lymphocytes isolated from two patients with ATL. In contrast, half-maximal inhibiton of protein synthesis in HTLV-uninfected, IL-2 receptor-negative T and B cell lines required 200- to 1,000-fold higher concentrations of anti-Tac-ricin A chain conjugates. Both unconjugated anti-Tac and immunoaffinity-purified IL-2 completely inhibited the toxic effects of anti-Tac-ricin A, confirming the specificity of the conjugate-IL-2 receptor interaction. Clonogenic assays demonstrated that anti-Tac-ricin A chain was able to eliminate >99.9% of an HTLV-1-infected T cell population at concentrations only marginally affecting IL-2 receptor-negative cells. The data presented demonstrate that anti-Tac-ricin A is selectively cytotoxic for HTLV-1-infected leukemic T cells in vitro and raises the future possibility of specific therapeutic intervention with immunotoxins in this disease.

Original languageEnglish (US)
Pages (from-to)1416-1421
Number of pages6
JournalBlood
Volume65
Issue number6
DOIs
StatePublished - 1985

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Kronke, M., Depper, J. M., Leonard, W. J., Vitetta, E. S., Waldmann, T. A., & Greene, W. C. (1985). Adult T cell leukemia: A potential target for ricin A chain immunotoxins. Blood, 65(6), 1416-1421. https://doi.org/10.1182/blood.v65.6.1416.bloodjournal6561416