Therapeutic activation of Valpha24+Vbeta11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity.
Human Valpha24+Vbeta11+ 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 Valpha24+Vbeta11+ 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 Valpha24+Vbeta11+ NKT cells and provide the first human in vivo evidence that Valpha24+Vbeta11+ 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 Valpha24+Vbeta11+ NKT cell memory produces faster, more vigorous secondary immune responses by innate and acquired immunity upon restimulation.
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D016130:Immunophenotyping; D007167:Immunotherapy / Q000009:adverse effects*; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human; D018664:Interleukin-12; D007371:Interferon-gamma