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Telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo
Version of Record online: 20 DEC 2005
Copyright © 2005 American Cancer Society
Volume 106, Issue 4, pages 759–764, 15 February 2006
How to Cite
Schmidt, J., Ryschich, E., Sievers, E., Schmidt-Wolf, I. G. H., Büchler, M. W. and Märten, A. (2006), Telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo. Cancer, 106: 759–764. doi: 10.1002/cncr.21655
- Issue online: 3 FEB 2006
- Version of Record online: 20 DEC 2005
- H.W. & J. Hector Foundation, Mannheim, Germany
- adoptive cell transfer;
- pancreatic carcinoma;
- antigen-specific T-cells;
- nonmyeloablative chemotherapy
Adoptive cell transfer is described as an innovative and challenging option for the treatment of malignant melanoma. In the current study, the generation and expansion of telomerase-specific T-cells for adoptive cell transfer and their use in a syngeneic pancreatic carcinoma mouse model was investigated.
Telomerase-specific T-cells were generated either in vitro by coculture of human lymphocytes with telomerase-peptide-pulsed dendritic cells or in vivo by injection of peptide plus adjuvant into C57BL/6 mice. Spleens were harvested after immunization and lymphocytes were expanded in the presence of feeder cells. T-cells were tested in vitro against human leukocyte antigen (HLA)-matched, telomerase-positive pancreatic carcinoma cells. Tumor-bearing (subcutaneous) mice pretreated with cyclophosphamide were injected intravenously with the expanded cells.
It was possible to generate and expand telomerase-specific T-cells with cytotoxic activity. The protocol did not work as well in the murine setting. However, adoptive cell transfer with murine antigen-specific T-cells delayed disease progression in tumor-bearing mice significantly.
Generation of antigen-specific T-cells is feasible; the expansion of these cells could be accomplished without loss of function. Antigen-specific T-cells demonstrated significant cytotoxic activity in a syngeneic, subcutaneous mouse model. However, further optimization of the expansion protocol is warranted. Cancer 2006. © 2005 American Cancer Society.