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 language | English (US) |
|---|---|
| Pages (from-to) | 2155-2166 |
| Number of pages | 12 |
| Journal | Clinical Cancer Research |
| Volume | 22 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
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 journal › Article
}
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 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.
AB - 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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UR - http://www.scopus.com/inward/citedby.url?scp=84969194975&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-15-2205
DO - 10.1158/1078-0432.CCR-15-2205
M3 - Article
VL - 22
SP - 2155
EP - 2166
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 9
ER -