Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia

T. Kiyokawa, K. Shirono, T. Hattori, H. Nishimura, K. Yamaguchi, J. C. Nichols, T. B. Strom, J. R. Murphy, K. Takatsuki

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

The inhibitory effect of a diphtheria toxin-related interleukin 2 fusion protein, IL-2-toxin, on protein synthesis in adult T-cell leukemia/lymphoma (ATL) cells was examined in vitro. Peripheral blood ATL cells from 12 patients (six acute type, four chronic type, and two smoldering type ATL) and the lymph node cells from three ATL patients (two acute type and one lymphoma type ATL) were examined. At a concentration of 10-8 M, IL-2-toxin inhibited protein synthesis by 60 to 98% in lymph node ATL cells, whereas protein synthesis in peripheral blood ATL cells was inhibited from 20 to 57% in acute type, and from 3 to 13% in chronic type. In contrast, IL-2-toxin had no measurable effect on T-cells from either patients with smoldering type ATL or normal controls. The cytopathic effects of IL-2-toxin were blocked by the addition of anti-CD25 monoclonal antibody, suggesting that the inhibition of protein synthesis in target cells was mediated by the IL-2 receptor (IL-2R). The degree of inhibition of protein synthesis, however, was not closely correlated with expression of CD25 antigen (low-affinity M(r) 55,000 glycoprotein, IL-2R, Tac antigen) on ATL cells. There was an apparent correlation between the degree of inhibition and the rate of protein synthesis in ATL cells. We demonstrate that ATL cells from patients with acute or lymphoma type disease were more sensitive to IL-2-toxin than cells from chronic or smoldering disease. These findings suggest that the high affinity IL-2R present on acute and lymphoma type ATL cells may serve as a target for therapy with this recombinant chimeric toxin.

Original languageEnglish
Pages (from-to)4042-4046
Number of pages5
JournalCancer Research
Volume49
Issue number14
Publication statusPublished - 1989

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'Cytotoxicity of interleukin 2-toxin toward lymphocytes from patients with adult T-cell leukemia'. Together they form a unique fingerprint.

Cite this