In vitro induction of a bladder cancer-specific T-cell response by mRNA-transfected dendritic cells.
OBJECTIVE
To design a tumor-specific immunotherapeutic strategy for treating tumors for which no specific antigens are described (such as bladder urothelial carcinoma), we attempted to activate tumor-specific T-cells by dendritic cells transfected with tumor-derived mRNA.


METHODS
Dendritic cells were generated from a patient's peripheral blood and loaded with mRNA derived from the urothelial carcinoma tissue of the same patient. Autologous T-cells were incubated twice on these dendritic cells and tested for their ability to lyse tumor cells.


RESULTS
Dendritic cells transfected with tumor-derived mRNA were able to activate T-cells that recognized autologous tumor cells. Cytotoxicity was around 26% for an effector:target ratio of 50:1. Tumor-infiltrating lymphocytes did not kill the autologous tumor cells in vitro, but after a single stimulation with the transfected dendritic cells, they induced tumor cell lysis of 35.7% at an effector:target ratio of 50:1.


CONCLUSIONS
These results indicate that dendritic cells transfected with tumor mRNA containing messages for one or more tumor antigens could serve for the ex vivo activation of effector T-cells or directly as vaccines for a wide range of human neoplasias.
Division of Diagnostics and Experimental Therapy, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
W E
WE
Schmitt
M J
MJ
Stassar
W
W
Schmitt
M
M
Little
B
B
Cochlovius
D000368:Aged; D017209:Apoptosis; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D002277:Carcinoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D002478:Cells, Cultured; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019459:Urothelium / Q000166:cytology / Q000473:pathology
D019496:Cancer Vaccines; D012333:RNA, Messenger