title: Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.
abstract: Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, alpha-galactosyl-ceramide (alpha-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of alpha-GalCer-pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-gamma inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to alpha-GalCer-loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.
authors.affiliation: Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Chang
authors.forename: Keren
authors.initials: K
authors.lastname: Osman
authors.forename: John
authors.initials: J
authors.lastname: Connolly
authors.forename: Anjli
authors.initials: A
authors.lastname: Kukreja
authors.forename: Joseph
authors.initials: J
authors.lastname: Krasovsky
authors.forename: Maggi
authors.initials: M
authors.lastname: Pack
authors.forename: Aisha
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Matthew
authors.initials: M
authors.lastname: Geller
authors.forename: Nancy
authors.initials: N
authors.lastname: Liu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Annable
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shay
authors.forename: Kelly
authors.initials: K
authors.lastname: Kirchhoff
authors.forename: Nobusuke
authors.initials: N
authors.lastname: Nishi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ando
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Hani
authors.initials: H
authors.lastname: Hassoun
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Madhav V
authors.initials: MV
authors.lastname: Dhodapkar
mesh_terms: D000328:Adult; D001774:Blood Chemical Analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D003587:Cytomegalovirus / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014611:Vaccination
chemical_list: D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D018664:Interleukin-12