Telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Schmidt
Jan
J
Department of Surgery, University of Heidelberg, Germany.
Ryschich
Eduard
E
Sievers
Elisabeth
E
Schmidt-Wolf
Ingo G H
IG
Büchler
Markus W
MW
Märten
Angela
A
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D002277:Carcinoma / Q000276:immunology / Q000628:therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003713:Dendritic Cells; D018450:Disease Progression; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D019098:Telomerase