Targeting activated lymphocytes with an entirely human immunotoxin analogue: Human pancreatic RNase1-human IL-12 fusion

Kyriakos Psarras, Masakazu Ueda, Minoru Tanabe, Masaki Kitajima, Sadakazu Aiso, Setsuko Komatsu, Masaharu Seno

研究成果: Article査読

28 被引用数 (Scopus)

抄録

A hybrid human protein was produced in E. coli by fusing the genes encoding human pancreatic RNase1 (hpRNase1) and human IL-2 (hIL-2). The recombinant hpRNase1-hIL-2 inhibited protein synthesis in HTLV-1-infected, malignant T cells, which hyperproduce high affinity IL-2 receptors, with an IC50 of 2 x 10-8 M, whereas no inhibition was detectable in control cells with lower affinity receptors. HpRNase1 alone had an IC50 of almost 10-3 M. A molar excess of hIL-2 blocked the protein synthesis inhibition dose-dependently. In a human mixed lymphocyte culture, hpRNase1-hIL-2 inhibited the proliferation of responder cells with potency comparable to that of cyclosporine, while non-effective doses of FK506 importantly improved its potency. Despite its short half-life in animals, hpRNase1-hIL-2 rapidly enters cells in a few minutes and arrests the protein translation in less than 10 h. Thus, hpRNase1-hIL-2 may be useful to selectively eliminate activated lymphocytes hyperproducing high affinity IL-2 receptors, as in allograft rejection, gaft-versus-host disease, autoimmune disorders, adult T cell leukaemia and other lymphoproliferative or retroviral malignancies including HIV infection, without inducing general immunosuppression. As an entirely human 'immunotoxin analogue' it may alleviate the dose limiting toxicity and immunogenicity of conventional immunotoxins. (C) 2000 Academic Press.

本文言語English
ページ(範囲)786-790
ページ数5
ジャーナルCytokine
12
6
DOI
出版ステータスPublished - 2000 6
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学
  • 生化学
  • 血液学
  • 分子生物学

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