title: Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells.
abstract: Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c(+) myeloid DCs, naturally circulating in the blood.
  
  
  
  Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous CD1c(+) myeloid DCs, activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens of tyrosinase and gp100.
  
  
  
  Our results show that therapeutic vaccination against melanoma with small amounts (3-10 × 10(6)) of myeloid DCs is feasible and without substantial toxicity. Four of 14 patients showed long-term progression-free survival (12-35 months), which directly correlated with the development of multifunctional CD8(+) T-cell responses in three of these patients. In particular, high CD107a expression, indicative for cytolytic activity, and IFNγ as well as TNFα and CCL4 production was observed. Apparently, these T-cell responses are essential to induce tumor regression and promote long-term survival by stalling tumor growth.
  
  
  
  We show that vaccination of metastatic melanoma patients with primary myeloid DCs is feasible and safe and results in induction of effective antitumor immune responses that coincide with improved progression-free survival. Clin Cancer Res; 22(9); 2155-66. ©2015 AACR.
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Gerty
authors.initials: G
authors.lastname: Schreibelt
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Kalijn F
authors.initials: KF
authors.lastname: Bol
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Harm
authors.initials: H
authors.lastname: Westdorp
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Florian
authors.initials: F
authors.lastname: Wimmers
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Erik H J G
authors.initials: EH
authors.lastname: Aarntzen
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Tjitske
authors.initials: T
authors.lastname: Duiveman-de Boer
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Mandy W M M
authors.initials: MW
authors.lastname: van de Rakt
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Scharenborg
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Annemiek J
authors.initials: AJ
authors.lastname: de Boer
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Pots
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Michel A M
authors.initials: MA
authors.lastname: Olde Nordkamp
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Tom G M
authors.initials: TG
authors.lastname: van Oorschot
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Jurjen
authors.initials: J
authors.lastname: Tel
authors.affiliation: Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors.forename: Gregor
authors.initials: G
authors.lastname: Winkels
authors.affiliation: Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Petry
authors.affiliation: Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Willeke A M
authors.initials: WA
authors.lastname: Blokx
authors.affiliation: Department of Dermatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: van Rossum
authors.affiliation: Department of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Marieke E B
authors.initials: ME
authors.lastname: Welzen
authors.affiliation: Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Roel D M
authors.initials: RD
authors.lastname: Mus
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Sandra A J
authors.initials: SA
authors.lastname: Croockewit
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Rutger H T
authors.initials: RH
authors.lastname: Koornstra
authors.affiliation: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Joannes F M
authors.initials: JF
authors.lastname: Jacobs
authors.affiliation: Department of Immunology, Netherlands Cancer Institute NKI-AVL, Amsterdam, the Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kelderman
authors.affiliation: Department of Immunology, Netherlands Cancer Institute NKI-AVL, Amsterdam, the Netherlands.
authors.forename: Christian U
authors.initials: CU
authors.lastname: Blank
authors.affiliation: Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Winald R
authors.initials: WR
authors.lastname: Gerritsen
authors.affiliation: Department of Medical Oncology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Department of Medical Oncology, Radboud University Medical Center, Nijmegen, the Netherlands. jolanda.devries@radboudumc.nl.
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D054407:Chemokine CCL4 / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009362:Neoplasm Metastasis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D054407:Chemokine CCL4; D052118:Lysosomal-Associated Membrane Protein 1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma