title: Immunologic and clinical effects of injecting mature peptide-loaded dendritic cells by intralymphatic and intranodal routes in metastatic melanoma patients.
abstract: OBJECTIVE
  A phase I/II trial was conducted to evaluate clinical and immunologic responses after intralymphatic and intranodal injections of mature dendritic cells.
  
  
  METHODS
  Fourteen patients with a metastatic melanoma received matured dendritic cells, loaded with Melan-A/MART-1 and/or NA17-A peptides and keyhole limpet hemocyanin. The cells were matured overnight with Ribomunyl, a toll-like receptor ligand, and IFN-gamma, which ensured the production of high levels of interleukin-12p70. Dendritic cells were injected at monthly intervals, first into an afferent lymphatic and then twice intranodally. Immunologic responses were monitored by tetramer staining of circulating CD8(+) lymphocytes and delayed-type hypersensitivity tests.
  
  
  RESULTS
  Dendritic cell vaccination induced delayed-type hypersensitivity reactivity toward NA17-A-pulsed, keyhole limpet hemocyanin-pulsed, and Melan-A-pulsed dendritic cells in 6 of 10, 4 of 11, and 3 of 9 patients, respectively. Four of the 12 patients analyzed by tetramer staining showed a significantly increased frequency of Melan-A-specific T cells, including one patient vaccinated only with NA17-A-pulsed dendritic cells. Furthermore, 2 of the 12 analyzed patients had a significant increase of NA17-A-specific T cells, including one immunized after an optional additional treatment course. No objective clinical response was observed. Two patients were stabilized at 4 and 10 months and three patients are still alive at 30, 39, and 48 months.
  
  
  CONCLUSIONS
  Injections into the lymphatic system of mature peptide-loaded dendritic cells with potential TH1 polarization capacities did not result in marked clinical results, despite immunologic responses in some patients. This highlights the need to improve our understanding of dendritic cell physiology.
authors.affiliation: Centre Eugène Marquis, Rennes, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lesimple
authors.forename: Eve-Marie
authors.initials: EM
authors.lastname: Neidhard
authors.forename: Virginie
authors.initials: V
authors.lastname: Vignard
authors.forename: Claudia
authors.initials: C
authors.lastname: Lefeuvre
authors.forename: Henri
authors.initials: H
authors.lastname: Adamski
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labarrière
authors.forename: André
authors.initials: A
authors.lastname: Carsin
authors.forename: Delphine
authors.initials: D
authors.lastname: Monnier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Collet
authors.forename: Gilles
authors.initials: G
authors.lastname: Clapisson
authors.forename: Brigitte
authors.initials: B
authors.lastname: Birebent
authors.forename: Irène
authors.initials: I
authors.lastname: Philip
authors.forename: Louis
authors.initials: L
authors.lastname: Toujas
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chokri
authors.forename: Véronique
authors.initials: V
authors.lastname: Quillien
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000032:analysis / Q000627:therapeutic use; D003713:Dendritic Cells / Q000737:chemistry / Q000637:transplantation*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D007272:Injections, Intralymphatic / Q000379:methods; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010455:Peptides