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; 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

doi:10.1158/1078-0432.CCR-15-2205

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

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 journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	2155-2166
Number of pages	12
Journal	Clinical Cancer Research
Volume	22
Issue number	9
DOIs	https://doi.org/10.1158/1078-0432.CCR-15-2205
Publication status	Published - 1 May 2016
Externally published	Yes

Keywords

Adult
Aged
Antigens, Neoplasm/immunology
CD8-Positive T-Lymphocytes/immunology
Cancer Vaccines/immunology
Chemokine CCL4/immunology
Dendritic Cells/immunology
Disease-Free Survival
Female
Humans
Interferon-gamma/immunology
Lysosomal-Associated Membrane Protein 1/immunology
Male
Melanoma/immunology
Middle Aged
Monocytes/immunology
Neoplasm Metastasis/immunology
Tumor Necrosis Factor-alpha/immunology
Vaccination/methods

Access to Document

10.1158/1078-0432.CCR-15-2205

Cite this

Schreibelt, G., Bol, K. F., Westdorp, H., Wimmers, F., Aarntzen, E. H. J. G., Duiveman-de Boer, T., van de Rakt, M. W. M. M., Scharenborg, N. M., de Boer, A. J., Pots, J. M., Olde Nordkamp, M. A. M., van Oorschot, T. G. M., Tel, J., Winkels, G., Petry, K., Blokx, W. A. M., van Rossum, M. M., Welzen, M. E. B., Mus, R. D. M., ... 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

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title = "Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells",

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 {\texttimes} 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. {\textcopyright}2015 AACR.",

keywords = "Adult, Aged, Antigens, Neoplasm/immunology, CD8-Positive T-Lymphocytes/immunology, Cancer Vaccines/immunology, Chemokine CCL4/immunology, Dendritic Cells/immunology, Disease-Free Survival, Female, Humans, Interferon-gamma/immunology, Lysosomal-Associated Membrane Protein 1/immunology, Male, Melanoma/immunology, Middle Aged, Monocytes/immunology, Neoplasm Metastasis/immunology, Tumor Necrosis Factor-alpha/immunology, Vaccination/methods",

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

note = "{\textcopyright}2015 American Association for Cancer Research.",

year = "2016",

month = may,

day = "1",

doi = "10.1158/1078-0432.CCR-15-2205",

language = "English",

volume = "22",

pages = "2155--2166",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "9",

}

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

TY - JOUR

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 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.

AB - 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.

KW - Adult

KW - Aged

KW - Antigens, Neoplasm/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - Cancer Vaccines/immunology

KW - Chemokine CCL4/immunology

KW - Dendritic Cells/immunology

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Interferon-gamma/immunology

KW - Lysosomal-Associated Membrane Protein 1/immunology

KW - Male

KW - Melanoma/immunology

KW - Middle Aged

KW - Monocytes/immunology

KW - Neoplasm Metastasis/immunology

KW - Tumor Necrosis Factor-alpha/immunology

KW - Vaccination/methods

U2 - 10.1158/1078-0432.CCR-15-2205

DO - 10.1158/1078-0432.CCR-15-2205

M3 - Article

C2 - 26712687

SN - 1078-0432

VL - 22

SP - 2155

EP - 2166

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 9

ER -

Effective Clinical Responses in Metastatic Melanoma Patients after Vaccination with Primary Myeloid Dendritic Cells

Abstract

Keywords

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