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 Croockewit & 8 others Rutger 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
StatePublished - May 1 2016
Externally publishedYes

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Myeloid Cells
Dendritic Cells
Melanoma
Vaccination
Disease-Free Survival
T-Lymphocytes
Neoplasms
Monophenol Monooxygenase
Neoplasm Antigens
Immunotherapy
Research Design
Survival
Therapeutics
Growth
In Vitro Techniques

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

Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. / Schreibelt, Gerty; Bol, Kalijn F.; Westdorp, Harm; Wimmers, Florian; Aarntzen, Erik H J G; Duiveman-De Boer, Tjitske; Van De Rakt, Mandy W M M; Scharenborg, Nicole M.; De Boer, Annemiek J.; Pots, Jeanette M.; Olde Nordkamp, Michel A M; Van Oorschot, Tom G M; Tel, Jurjen; Winkels, Gregor; Petry, Katja; Blokx, Willeke A M; Van Rossum, Michelle M.; Welzen, Marieke E B; Mus, Roel D M; Croockewit, Sandra A J; Koornstra, Rutger H T; Jacobs, Joannes F M; Kelderman, Sander; Blank, Christian U.; Gerritsen, Winald R.; Punt, Cornelis J A; Figdor, Carl G.; De Vries, I. Jolanda M.

In: Clinical Cancer Research, Vol. 22, No. 9, 01.05.2016, p. 2155-2166.

Research output: Contribution to journalArticle

Schreibelt, G, Bol, KF, Westdorp, H, Wimmers, F, Aarntzen, EHJG, Duiveman-De Boer, T, Van De Rakt, MWMM, Scharenborg, NM, De Boer, AJ, Pots, JM, Olde Nordkamp, MAM, Van Oorschot, TGM, Tel, J, Winkels, G, Petry, K, Blokx, WAM, Van Rossum, MM, Welzen, MEB, Mus, RDM, Croockewit, SAJ, Koornstra, RHT, Jacobs, JFM, Kelderman, S, Blank, CU, Gerritsen, WR, Punt, CJA, Figdor, CG & De Vries, IJM 2016, 'Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells', Clinical Cancer Research, vol. 22, no. 9, pp. 2155-2166. https://doi.org/10.1158/1078-0432.CCR-15-2205
Schreibelt, Gerty ; Bol, Kalijn F. ; Westdorp, Harm ; Wimmers, Florian ; Aarntzen, Erik H J G ; Duiveman-De Boer, Tjitske ; Van De Rakt, Mandy W M M ; Scharenborg, Nicole M. ; De Boer, Annemiek J. ; Pots, Jeanette M. ; Olde Nordkamp, Michel A M ; Van Oorschot, Tom G M ; Tel, Jurjen ; Winkels, Gregor ; Petry, Katja ; Blokx, Willeke A M ; Van Rossum, Michelle M. ; Welzen, Marieke E B ; Mus, Roel D M ; Croockewit, Sandra A J ; Koornstra, Rutger H T ; Jacobs, Joannes F M ; Kelderman, Sander ; Blank, Christian U. ; Gerritsen, Winald R. ; Punt, Cornelis J A ; Figdor, Carl G. ; De Vries, I. Jolanda M. / Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 9. pp. 2155-2166.
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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.",
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T1 - Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells

AU - Schreibelt, Gerty

AU - Bol, Kalijn F.

AU - Westdorp, Harm

AU - Wimmers, Florian

AU - Aarntzen, Erik H J G

AU - Duiveman-De Boer, Tjitske

AU - Van De Rakt, Mandy W M M

AU - Scharenborg, Nicole M.

AU - De Boer, Annemiek J.

AU - Pots, Jeanette M.

AU - Olde Nordkamp, Michel A M

AU - Van Oorschot, Tom G M

AU - Tel, Jurjen

AU - Winkels, Gregor

AU - Petry, Katja

AU - Blokx, Willeke A M

AU - Van Rossum, Michelle M.

AU - Welzen, Marieke E B

AU - Mus, Roel D M

AU - Croockewit, Sandra A J

AU - Koornstra, Rutger H T

AU - Jacobs, Joannes F M

AU - Kelderman, Sander

AU - Blank, Christian U.

AU - Gerritsen, Winald R.

AU - Punt, Cornelis J A

AU - Figdor, Carl G.

AU - De Vries, I. Jolanda M

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

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