Natural Human Plasmacytoid Dendritic Cells Induce Antigen-Specific T-Cell Responses in Melanoma Patients

被引:281
作者
Tel, Jurjen [1 ]
Aarntzen, Erik H. J. G. [1 ,2 ]
Baba, Tetsuro [7 ]
Schreibelt, Gerty [1 ]
Schulte, Barbara M. [1 ]
Benitez-Ribas, Daniel [1 ]
Boerman, Otto C. [5 ]
Croockewit, Sandra [6 ]
Oyen, Wim J. G. [5 ]
van Rossum, Michelle [4 ]
Winkels, Gregor [8 ]
Coulie, Pierre G. [7 ]
Punt, Cornelis J. A. [2 ]
Figdor, Carl G. [1 ]
de Vries, I. Jolanda M. [1 ,2 ,3 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Dept Tumor Immunol, NL-6500 HB Nijmegen, Netherlands
[2] Radboud Univ Nijmegen, Med Ctr, Dept Med Oncol, NL-6500 HB Nijmegen, Netherlands
[3] Radboud Univ Nijmegen, Med Ctr, Dept Pediat Oncol, NL-6500 HB Nijmegen, Netherlands
[4] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, NL-6500 HB Nijmegen, Netherlands
[5] Radboud Univ Nijmegen, Med Ctr, Dept Nucl Med, NL-6500 HB Nijmegen, Netherlands
[6] Radboud Univ Nijmegen, Med Ctr, Dept Hematol, NL-6500 HB Nijmegen, Netherlands
[7] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium
[8] Miltenyi Biotec GmbH, Bergisch Gladbach, Germany
关键词
INFLAMED LYMPH-NODES; IN-VIVO; TUMOR-REGRESSION; INFLUENZA-VIRUS; VACCINATION; MIGRATION; INTERFERON; MATURATION; VACCINES; LYMPHOCYTES;
D O I
10.1158/0008-5472.CAN-12-2583
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Vaccination against cancer by using dendritic cells has for more than a decade been based on dendritic cells generated ex vivo from monocytes or CD34(+) progenitors. Here, we report on the first clinical study of therapeutic vaccination against cancer using naturally occurring plasmacytoid dendritic cells (pDC). Fifteen patients with metastatic melanoma received intranodal injections of pDCs activated and loaded with tumor antigen-associated peptides ex vivo. In vivo imaging showed that administered pDCs migrated and distributed over multiple lymph nodes. Several patients mounted antivaccine CD4(+) and CD8(+) T-cell responses. Despite the limited number of administered pDCs, an IFN signature was observed after each vaccination. These results indicate that vaccination with naturally occurring pDC is feasible with minimal toxicity and that in patients with metastatic melanoma, it induces favorable immune responses. Cancer Res; 73(3); 1063-75. (C) 2012 AACR.
引用
收藏
页码:1063 / 1075
页数:13
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