Natural human plasmacytoid dendritic cells induce antigen-specific T-cell responses in melanoma patients.
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.
Department of Tumor Immunology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Jurjen
J
Tel
Erik H J G
EH
Aarntzen
Tetsuro
T
Baba
Gerty
G
Schreibelt
Barbara M
BM
Schulte
Daniel
D
Benitez-Ribas
Otto C
OC
Boerman
Sandra
S
Croockewit
Wim J G
WJ
Oyen
Michelle
M
van Rossum
Gregor
G
Winkels
Pierre G
PG
Coulie
Cornelis J A
CJ
Punt
Carl G
CG
Figdor
I Jolanda M
IJ
de Vries
D000328:Adult; D000368:Aged; D000917:Antibody Formation; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007372:Interferons / Q000235:genetics; D008213:Lymphocyte Activation; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D007372:Interferons