title: Route of administration modulates the induction of dendritic cell vaccine-induced antigen-specific T cells in advanced melanoma patients.
abstract: OBJECTIVE
  It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine.
  
  
  METHODS
  HLA-A2.1(+) melanoma patients scheduled for regional lymph node dissection were vaccinated four times biweekly via intradermal or intranodal injection with 12 × 10⁶ to 17 × 10⁶ mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH). Half of the patients also received low-dose IL-2 (9 MIU daily for 7 days starting 3 days after each vaccination). KLH-specific B- and T-cell responses were monitored in blood. gp100- and tyrosinase-specific T-cell responses were monitored in blood by tetramer analysis and in biopsies from delayed-type hypersensitivity (DTH) skin tests by tetramer and functional analyses with (51)Cr release assays or IFNγ release, following coculture with peptide-pulsed T2 cells or gp100- or tyrosinase-expressing tumor cells.
  
  
  RESULTS
  In 19 of 43 vaccinated patients, functional tumor antigen-specific T cells could be detected. Although significantly more DCs migrated to adjacent lymph nodes upon intranodal vaccination, this was also highly variable with a complete absence of migration in 7 of 24 intranodally vaccinated patients. Intradermal vaccinations proved superior in inducing functional tumor antigen-specific T cells. Coadministration of IL-2 did not further augment the antigen-specific T-cell response but did result in higher regulatory T-cell frequencies.
  
  
  CONCLUSIONS
  Intradermal vaccination resulted in superior antitumor T-cell induction when compared with intranodal vaccination. No advantage of additional IL-2 treatment could be shown.
authors.affiliation: Department of Medical Oncology,Nijmegen Centre for Molecular Life Sciences, and Laboratory of Medical Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Lesterhuis
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Gerty
authors.initials: G
authors.lastname: Schreibelt
authors.forename: Annechien J A
authors.initials: AJ
authors.lastname: Lambeck
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.forename: Joannes F M
authors.initials: JF
authors.lastname: Jacobs
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Scharenborg
authors.forename: Mandy W M M
authors.initials: MW
authors.lastname: van de Rakt
authors.forename: Annemiek J
authors.initials: AJ
authors.lastname: de Boer
authors.forename: Sandra
authors.initials: S
authors.lastname: Croockewit
authors.forename: Michelle M
authors.initials: MM
authors.lastname: van Rossum
authors.forename: Roel
authors.initials: R
authors.lastname: Mus
authors.forename: Wim J G
authors.initials: WJ
authors.lastname: Oyen
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Sophie
authors.initials: S
authors.lastname: Lucas
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology*; D004333:Drug Administration Routes; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D015789:HLA-A2 Antigen / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D007271:Injections, Intradermal; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015789:HLA-A2 Antigen; D007376:Interleukin-2; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin