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

作者: K. Takatsuki , K. Shirono , T. Hattori , K. Yamaguchi , T. Kiyokawa

DOI:

关键词:

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

参考文章(22)
T Hattori, T Uchiyama, T Toibana, K Takatsuki, H Uchino, Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies Blood. ,vol. 58, pp. 645- 647 ,(1981) , 10.1182/BLOOD.V58.3.645.BLOODJOURNAL583645
J Fukumori, K Onoue, N Arima, Y Daitoku, H Tanaka, K Fujimoto, K Matsushita, Y Yamamoto, K Kojima, S Ohgaki, Heterogeneity in response to interleukin 2 and interleukin 2-producing ability of adult T cell leukemic cells. Journal of Immunology. ,vol. 138, pp. 3069- 3074 ,(1987)
Fumio Kawano, Kazunari Yamaguchi, Hiromichi Nishimura, Hiroyuki Tsuda, Kiyoshi Takatsuki, Variation in the clinical courses of adult T‐cell leukemia Cancer. ,vol. 55, pp. 851- 856 ,(1985) , 10.1002/1097-0142(19850215)55:4<851::AID-CNCR2820550424>3.0.CO;2-J
M Sharon, R. Klausner, B. Cullen, R Chizzonite, W. Leonard, Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science. ,vol. 234, pp. 859- 863 ,(1986) , 10.1126/SCIENCE.3095922
J. R. Murphy, W. Bishai, M. Borowski, A. Miyanohara, J. Boyd, S. Nagle, Genetic construction, expression, and melanoma-selective cytotoxicity of a diphtheria toxin-related alpha-melanocyte-stimulating hormone fusion protein. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 83, pp. 8258- 8262 ,(1986) , 10.1073/PNAS.83.21.8258
M. Tsudo, R. W. Kozak, C. K. Goldman, T. A. Waldmann, Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex Proceedings of the National Academy of Sciences of the United States of America. ,vol. 83, pp. 9694- 9698 ,(1986) , 10.1073/PNAS.83.24.9694
M. Yoshida, I. Miyoshi, Y. Hinuma, Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease Proceedings of the National Academy of Sciences of the United States of America. ,vol. 79, pp. 2031- 2035 ,(1982) , 10.1073/PNAS.79.6.2031
Y. Hinuma, K. Nagata, M. Hanaoka, M. Nakai, T. Matsumoto, K. I. Kinoshita, S. Shirakawa, I. Miyoshi, Adult T-cell leukemia : antigen in an ATL cell line and detection of antibodies to the antigen in human sera Proceedings of the National Academy of Sciences of the United States of America. ,vol. 78, pp. 6476- 6480 ,(1981) , 10.1073/PNAS.78.10.6476
Mitchell Dukovich, Yuji Wano, Le thi Rich Thuy, Paul Katz, Bryan R. Cullen, John H. Kehrl, Warner C. Greene, A second human interleukin-2 binding protein that may be a component of high-affinity interleukin-2 receptors Nature. ,vol. 327, pp. 518- 522 ,(1987) , 10.1038/327518A0