In vitro induction of a bladder cancer-specific T-cell response by mRNA-transfected dendritic cells

PMID: 11260867
Journal: Journal of cancer research and clinical oncology (volume: 127, issue: 3, J. Cancer Res. Clin. Oncol. 2001;127(3):203-6)
Published: 2001-01-01

Schmitt WE, Stassar MJ, Schmitt W, Little M, Cochlovius B


PURPOSE: 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.