title: Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms.
abstract: BACKGROUND
  CD1d is a monomorphic antigen presentation molecule expressed in several hematologic malignancies. Alpha-galactosylceramide (alpha-GalCer) is a glycolipid that can be presented to cytotoxic CD1d-restricted T cells. These reagents represent a potentially powerful tool for cell mediated immunotherapy.
  
  
  METHODS
  We set up an experimental model to evaluate the use of adoptively transferred cytotoxic CD1d-restricted T cells and alpha-GalCer in the treatment of mice engrafted with CD1d(+) lymphoid neoplastic cells. To this end the C1R cell line was transfected with CD1c or CD1d molecules. In addition, upon retroviral infection firefly luciferase was expressed on C1R transfected cell lines allowing the evaluation of tumor growth in xenografted immunodeficient NOD/SCID mice.
  
  
  RESULTS
  The C1R-CD1d cell line was highly susceptible to specific CD1d-restricted T cell cytotoxicity in the presence alpha-GalCer in vitro. After adoptive transfer of CD1d-restricted T cells and alpha-GalCer to mice engrafted with both C1R-CD1c and C1R-CD1d, a reduction in tumor growth was observed only in CD1d(+) masses. In addition, CD1d-restricted T-cell treatment plus alpha-GalCer eradicated small C1R-CD1d(+) nodules. Immunohistochemical analysis revealed that infiltrating NKT cells were mainly observed in CD1d nodules.
  
  
  CONCLUSIONS
  Our results indicate that ex vivo expanded cytotoxic CD1d-restricted T cells and alpha-GalCer may represent a new immunotherapeutic tool for treatment of CD1d(+) hematologic malignancies.
authors.affiliation: Human Anatomy Section, Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Bagnara
authors.forename: Adalberto
authors.initials: A
authors.lastname: Ibatici
authors.forename: Mirko
authors.initials: M
authors.lastname: Corselli
authors.forename: Nadia
authors.initials: N
authors.lastname: Sessarego
authors.forename: Claudya
authors.initials: C
authors.lastname: Tenca
authors.forename: Amleto
authors.initials: A
authors.lastname: De Santanna
authors.forename: Andrea
authors.initials: A
authors.lastname: Mazzarello
authors.forename: Antonio
authors.initials: A
authors.lastname: Daga
authors.forename: Renzo
authors.initials: R
authors.lastname: Corvò
authors.forename: Giulio
authors.initials: G
authors.lastname: De Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.forename: Ermanno
authors.initials: E
authors.lastname: Ciccone
authors.forename: Franco
authors.initials: F
authors.lastname: Fais
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007107:Immune System; D007150:Immunohistochemistry / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000473:pathology*
chemical_list: D055610:Antigens, CD1d