title: A phase I study of in vitro expanded natural killer T cells in patients with advanced and recurrent non-small cell lung cancer.
abstract: OBJECTIVE
  Human Valpha24 natural killer T (Valpha24 NKT) cells bearing an invariant Valpha24JalphaQ antigen receptor are activated by a glicolipid ligand alpha-galactosylceramide (alphaGalCer; KRN7000) in a CD1d-dependent manner. The human Valpha24 NKT cells activated with alphaGalCer and interleukin-2 have been shown to produce large amounts of cytokines, such as IFN-gamma, and also exerting a potent killing activity against various tumor cell lines. We did a phase I study with autologous activated Valpha24 NKT cell therapy.
  
  
  METHODS
  Patients with advanced or recurrent non-small cell lung cancer received i.v. injections of activated Valpha24 NKT cells (level 1: 1 x 10(7)/m2 and level 2: 5 x 10(7)/m2) to test the safety, feasibility, and clinical response of this therapeutic strategy. Immunomonitoring was also done in all cases.
  
  
  RESULTS
  Six patients were enrolled in this study. No severe adverse events were observed during this study in any patients. After the first and second injection of activated Valpha24 NKT cells, an increased number of peripheral blood Valpha24 NKT cells was observed in two of three cases receiving a level 2 dose of activated Valpha24 NKT cells. The number of IFN-gamma-producing cells in peripheral blood mononuclear cells increased after the administration of activated Valpha24 NKT cells in all three cases receiving the level 2 dose. No patient was found to meet the criteria for either a partial or a complete response.
  
  
  CONCLUSIONS
  The clinical trial with activated Valpha24 NKT cell administration was well tolerated and carried out safely with minor adverse events even in patients with advanced diseases.
authors.affiliation: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Aki
authors.initials: A
authors.lastname: Ishikawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ishikawa
authors.forename: Mizuto
authors.initials: M
authors.lastname: Otsuji
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iizasa
authors.forename: Hideki
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimizu
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Horiguchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Fujii
authors.forename: Masaru
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nakayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D008175:Lung Neoplasms / Q000628:therapy*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion / Q000009:adverse effects*; D008875:Middle Aged; D018579:Patient Selection; D012008:Recurrence