A new immunomodulating compound (AS-101) with potential therapeutic application.
There has been interest in the potential of synthetic compounds to modify immune responses by imitation of cytokine action. Direct administration of interleukin 2 (IL-2) in conjunction with adoptive transfer of lymphokine activated killer cells has been used in the treatment of cancer, but there are toxic effects resulting from the high doses of IL-2 required. 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.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D005030:Ethylenes / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D007167:Immunotherapy; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008175:Lung Neoplasms / Q000628:therapy*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011971:Receptors, Immunologic / Q000096:biosynthesis; D015375:Receptors, Interleukin-2; D013691:Tellurium / Q000494:pharmacology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D005030:Ethylenes; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; D013691:Tellurium