Journal article

Sequential activation of NKT cells and NK cells provides effective innate immunotherapy of cancer

MJ Smyth, ME Wallace, SL Nutt, H Yagita, DI Godfrey, Y Hayakawa

JOURNAL OF EXPERIMENTAL MEDICINE | ROCKEFELLER UNIV PRESS | Published : 2005

Abstract

The CD1d reactive glycolipid, alpha-galactosylceramide (alpha-GalCer), potently activates T cell receptor-alpha type I invariant NKT cells that secondarily stimulate the proliferation and activation of other leukocytes, including NK cells. Here we report a rational approach to improving the antitumor activity of alpha-GalCer by using delayed interleukin (IL)-21 treatment to mature the alpha-GalCer-expanded pool of NK cells into highly cytotoxic effector cells. In a series of experimental and spontaneous metastases models in mice, we demonstrate far superior antitumor activity of the alpha-GalCer/IL-21 combination above either agent alone. Superior antitumor activity was critically dependent ..

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