Therapeutic activation of V24+V11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity
From the Queensland Institute of Medical Research, Brisbane, Australia; Department of Medicine, University of Queensland, Brisbane, Australia; Departments of Oncology and Nuclear Medicine, Royal Brisbane Hospital, Brisbane, Australia; Yokohama City University School of Medicine, Yokohama, Japan; and Japanese Red Cross, Tokyo, Japan.7vl, http://www.100md.com
Human V{alpha} 24+V{beta} 11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by {alpha} -galactosylceramide ({alpha} -GalCer) (KRN7000) presented by CD1d on antigen-presenting cells. Preclinical models show that activation of V{alpha} 24+V{beta} 11+ NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with {alpha} -GalCer–pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on V{alpha} 24+V{beta} 11+ NKT cells and provide the first human in vivo evidence that V{alpha} 24+V{beta} 11+ NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-{gamma} . We present the first clinical evidence that V{alpha} 24+V{beta} 11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.(Mie Nieda Miki Okai Andrea Tazbirkova Henry Lin Ayako Yamaura Kazuki Ide Rick Abraham Takeo Juji Dav)
Human V{alpha} 24+V{beta} 11+ natural killer T (NKT) cells are a distinct CD1d-restricted lymphoid subset specifically and potently activated by {alpha} -galactosylceramide ({alpha} -GalCer) (KRN7000) presented by CD1d on antigen-presenting cells. Preclinical models show that activation of V{alpha} 24+V{beta} 11+ NKT cells induces effective antitumor immune responses and potentially important secondary immune effects, including activation of conventional T cells and NK cells. We describe the first clinical trial of cancer immune therapy with {alpha} -GalCer–pulsed CD1d-expressing dendritic cells. The results show that this therapy has substantial, rapid, and highly reproducible specific effects on V{alpha} 24+V{beta} 11+ NKT cells and provide the first human in vivo evidence that V{alpha} 24+V{beta} 11+ NKT cell stimulation leads to activation of both innate and acquired immunity, resulting in modulation of NK, T-, and B-cell numbers and increased serum interferon-{gamma} . We present the first clinical evidence that V{alpha} 24+V{beta} 11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.(Mie Nieda Miki Okai Andrea Tazbirkova Henry Lin Ayako Yamaura Kazuki Ide Rick Abraham Takeo Juji Dav)