Abstract
There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action1,2. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer3,4, but there are toxic effects resulting from the high doses of IL-2 required3,5. We have developed a new synthetic compound, ammonium tri-chloro(dioxoethylene-O,O′-)tellurate (AS-101), which has immunomodulating properties and minimal toxicity. The effects of AS-101 on the activation and function of immunocompetent cells have been assessed. We have found that AS-101 induces proliferation and IL-2 production by human lymphocytes in vitro, and enhances the production of IL-2 and colony-stimulating factor by mouse spleen cells. Splenocytes of BALB/c mice injected with AS-101 increased production of IL-2 and CSF in vitro in the presence of mitogen. Mononuclear cells of normal donors acquired responsiveness to recombinant IL-2 and bound monoclonal antibody to IL-2 receptor after incubation with AS-101. Splenocytes of mice treated in vivo with AS-101 expressed high levels of IL-2 receptor. The stimulation of lymphocytes by AS-101 apparently involves an increase in intracellular free calcium. AS-101 administered systemically to mice mediated antitumour effects which could be attributable to its immunomodulatory properties. In addition, AS-101 could directly enhance the ratio of OKT4 to OKT8-positive cells in cultured mononuclear cells from AIDS (acquired immune deficiency syndrome) patients. These results indicate that AS-101 is potentially useful in the treatment of clinical conditions involving immunosuppression.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
1. Chirigos, M. A. & Talmadge, J. E. Springer Seminar Immunophatol. 8, 327-346 (1985). 2. Fenichel, R. L. & Chirigos, M. A. in Immune Modulation Agents and their Mechanisms, Vol. 25 (eds Fenichel, R. & Chirigos, M. A.) (Dekker, New York, 1985). 3. Rosenberg, S. A. et al. New Engl. J. Med. 313, 1485-1492 (1985). 4. Mule, J. J., Shu, S., Schwarz, S. L. & Rosenberg, S. A. Science 225, 1487-1489 (1984). 5. Lotze, M. T. et al J. Immun. 135, 2865-2875 (1985). 6. Rosenberg, B. Cancer 55, 2303-2316 (1985). 7. Brown, R. L., Griffith, R. L., Ruscetti, F. W. & Rabin, H. Cell. Immun. 92, 14-21 (1985). 8. Goodman, M. G. & Weigle, W. O. / Immun. 126, 20-26 (1981). 9. Farrar, J. J. et al. Immunol. Rev. 63, 129-166 (1982). 10. Oppenheim, J. J. & Rosenstreich, D. L. Prog. Allergy 20, 65-194 (1976). 11. Apte, R. N., Heller, E., Hertogs, C. F. & Pluznik, D. H. in Experimental Hematology Today (eds Baum, S. J. & Ledney, D. G.) 213-220 (Springer, New York, 1978). 12. Pluznik, D. H. & Sachs, L. J. cell comp. Physiol. 66, 319-329 (1965). 13. Bradley, T. R. & Metcalf, D. J. Aust. J. exp. Biol. med. Sci. 44, 287-299 (1966). 14. Mills, G. B., Cheung, R. K., Grinstein, S. & Gelfand, E. W. J. Immun. 134,1640-1643 (1985). 15. Truneh, A., Albert, F., Golstein, P. & Schmitt-Verhulst, A.-M. Nature 313, 318-320 (1985). 16. Gelfand, E. W., Cheung, R. K., Grinstein, S. & Mills, G. B. Eur. J. Immun. 16,907-912 (1986). 17. Manger, B., Hardy, K. J., Weiss, A. & Stobo, J. D. J. din. Invest. 77, 1501-1506 (1986). 18. Kay, J. E. & Benzie, C. R. Immunology 57, 195-199 (1986). 19. Gelfand, E. W., Cheung, R. K. & Mills, G. B. / Immun. 138, 1115-1120 (1987). 20. Robb, R. J., Munk, A. & Smith, K. A. / exp. Med. 154, 1455-1474 (1981). 21. Smith, K. A., Wang, H. M. & Cantrel, D. A. in Progress in Immunology (eds Yamamura, V. Y. & Tada, T.) 269 (Academic, New York, 1983). 22. Cantrel, D. A. & Smith, K. A. /. exp. Med. 158, 1895-1911 (1983). 23. Rosenberg, S. A., Mule, J. J., Spiess, P. J., Reichert, C. M. & Schwarz, S. L. / exp. Med. 161, 1169-1188 (1985). 24. Grabstein, K. H. et al. Science 232, 506-508 (1986). 25. Satoh, M., Ichimura, O., Mitsuno, T., Koyima, E. & Osawa, T. / pharm. Dyn. 5, 818-828 (1982). 26. Klein, A. & Shoham, J. Cancer Res. 41, 3217-3221 (1981). 27. Gelfand, E. W., Cheung, R. K. & Grinstein, S. /. cell Physiol. 121, 533-539 (1984). 28. Tsein, R. Y., Pozzan, T. & Rink, T. J. J. Cell Biol. 94, 325-334 (1982). 29. Rosenberg, S. A., Spiess, P. J. & Schwarz, S. Transplantation 35, 631-634 (1983). 30. Chang, A. E., Hyatt, C. L. & Rosenberg, S. A. /. biol. Resp. Mod. 3, 561-572 (1984). 31. Rosenberg, S. A., Spiess, P. & Lafreniere, R. Science 233, 1318-1321 (1986). 32. Bindon, C. et al. Br. J. Cancer 47, 123-133 (1983). 33. Lotze, M. T., Frana, W., Sharrow, S. O., Robb, R. J. & Rosenberg, S. A. J. Immun. 134, 157-166 (1985). 34. Sredni, B., Friedman, M. M., Bland, C. E. & Metcalfe, D. D. /. Immun. 131,915-922 (1983). 35. Tsudo, M., Uchiyama, T., Takatsuki, K., Uchino, H. & Yodoi, J. J. Immun. 129, 592-595 (1982). 36. Lillehoj, H. S., Malek, T. R. & Shevach, E. M. J. Immun. 133, 244-250 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sredni, B., Caspi, R., Klein, A. et al. A new immunomodulating compound (AS-101) with potential therapeutic application. Nature 330, 173–176 (1987). https://doi.org/10.1038/330173a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/330173a0
This article is cited by
-
Synthesis and screening for anticancer activity of two novel telluro-amino acids: 1,3-Tellurazolidine-4-carboxylic acid and tellurohomocystine
Amino Acids (2023)
-
Screening of AS101 analog, organotellurolate (IV) compound 2 for its in vitro biocompatibility, anticancer, and antibacterial activities
Amino Acids (2023)
-
Diphenyl Ditelluride Induces Anxiogenic-Like Behavior in Rats by Reducing Glutamate Uptake
Biological Trace Element Research (2014)
-
Antibacterial effects of the tellurium compound OTD on E. coli isolates
Archives of Microbiology (2014)
-
Tellurium Compound AS101 Ameliorates Experimental Autoimmune Encephalomyelitis by VLA-4 Inhibition and Suppression of Monocyte and T Cell Infiltration into the CNS
NeuroMolecular Medicine (2014)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.