Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells

Gerty Schreibelt, Kalijn F. Bol, Harm Westdorp, Florian Wimmers, Erik H J G Aarntzen, Tjitske Duiveman-De Boer, Mandy W M M Van De Rakt, Nicole M. Scharenborg, Annemiek J. De Boer, Jeanette M. Pots, Michel A M Olde Nordkamp, Tom G M Van Oorschot, Jurjen Tel, Gregor Winkels, Katja Petry, Willeke A M Blokx, Michelle M. Van Rossum, Marieke E B Welzen, Roel D M Mus, Sandra A J CroockewitRutger H T Koornstra, Joannes F M Jacobs, Sander Kelderman, Christian U. Blank, Winald R. Gerritsen, Cornelis J A Punt, Carl G. Figdor, I. Jolanda M De Vries

Research output: Contribution to journalArticle

Abstract

Purpose: Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocytederived DCs, which require extensive in vitro manipulation. Here, we report on a clinical study exploiting primary CD1c+ myeloid DCs, naturally circulating in the blood. Experimental Design: 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. Results: Our results show that therapeutic vaccination against melanoma with small amounts (3-10 × 106) 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)2155-2166
Number of pages12
JournalClinical Cancer Research
Volume22
Issue number9
DOIs
Publication statusPublished - May 1 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Schreibelt, G., Bol, K. F., Westdorp, H., Wimmers, F., Aarntzen, E. H. J. G., Duiveman-De Boer, T., ... De Vries, I. J. M. (2016). Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. Clinical Cancer Research, 22(9), 2155-2166. https://doi.org/10.1158/1078-0432.CCR-15-2205