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

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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
StatePublished - 1985

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Ricin
Immunotoxins
Adult T Cell Leukemia Lymphoma
T-cells
Interleukin-2 Receptors
Deltaretrovirus
T-Lymphocytes
Viruses
Cell Line
Proteins
Poisons
Virus Diseases
Interleukin-2
Leukemia
B-Lymphocytes
Antibodies
Cytotoxicity
Population
Assays
Neoplasms

ASJC Scopus subject areas

  • Hematology

Cite this

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.

Adult T cell leukemia : A potential target for ricin A chain immunotoxins. / Kronke, M.; Depper, J. M.; Leonard, W. J.; Vitetta, E. S.; Waldmann, T. A.; Greene, W. C.

In: Blood, Vol. 65, No. 6, 1985, p. 1416-1421.

Research output: Contribution to journalArticle

Kronke, M, Depper, JM, Leonard, WJ, Vitetta, ES, Waldmann, TA & Greene, WC 1985, 'Adult T cell leukemia: A potential target for ricin A chain immunotoxins', Blood, vol. 65, no. 6, pp. 1416-1421.
Kronke M, Depper JM, Leonard WJ, Vitetta ES, Waldmann TA, Greene WC. Adult T cell leukemia: A potential target for ricin A chain immunotoxins. Blood. 1985;65(6):1416-1421.
Kronke, M. ; Depper, J. M. ; Leonard, W. J. ; Vitetta, E. S. ; Waldmann, T. A. ; Greene, W. C. / Adult T cell leukemia : A potential target for ricin A chain immunotoxins. In: Blood. 1985 ; Vol. 65, No. 6. pp. 1416-1421.
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