title: Telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Surgery, University of Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Eduard
authors.initials: E
authors.lastname: Ryschich
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sievers
authors.forename: Ingo G H
authors.initials: IG
authors.lastname: Schmidt-Wolf
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Angela
authors.initials: A
authors.lastname: Märten
mesh_terms: 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
chemical_list: D000951:Antigens, Neoplasm; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D019098:Telomerase