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.
N1 - ©2015 American Association for Cancer Research.
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 - Journal Article
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 -
