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
Y1 - 2016
N2 - 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. 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. 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. 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 - 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. 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. 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. 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
U2 - https://doi.org/10.1158/1078-0432.CCR-15-2205
DO - https://doi.org/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 -