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

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Abstract

PURPOSE: 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.

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 × 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.

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. Clin Cancer Res; 22(9); 2155-66. ©2015 AACR.

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

Keywords

  • Journal Article

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    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