PMID- 16369992
OWN - NLM
STAT- MEDLINE
DCOM- 20060328
LR  - 20131121
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 106
IP  - 4
DP  - 2006 Feb 15
TI  - Telomerase-specific T-cells kill pancreatic tumor cells in vitro and in vivo.
PG  - 759-64
AB  - 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.
CI  - Copyright 2006 American Cancer Society.
FAU - Schmidt, Jan
AU  - Schmidt J
AD  - Department of Surgery, University of Heidelberg, Germany.
FAU - Ryschich, Eduard
AU  - Ryschich E
FAU - Sievers, Elisabeth
AU  - Sievers E
FAU - Schmidt-Wolf, Ingo G H
AU  - Schmidt-Wolf IG
FAU - Buchler, Markus W
AU  - Buchler MW
FAU - Marten, Angela
AU  - Marten A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - *Adoptive Transfer
MH  - Animals
MH  - Antigens, Neoplasm
MH  - Antineoplastic Agents, Alkylating/administration & dosage
MH  - Carcinoma/immunology/*therapy
MH  - Cyclophosphamide/administration & dosage
MH  - Dendritic Cells
MH  - Disease Progression
MH  - Infusions, Intravenous
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pancreatic Neoplasms/immunology/*therapy
MH  - Spleen/cytology
MH  - T-Lymphocytes/enzymology/*immunology
MH  - Telomerase/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2005/12/22 09:00
MHDA- 2006/03/29 09:00
CRDT- 2005/12/22 09:00
PHST- 2005/12/22 09:00 [pubmed]
PHST- 2006/03/29 09:00 [medline]
PHST- 2005/12/22 09:00 [entrez]
AID - 10.1002/cncr.21655 [doi]
PST - ppublish
SO  - Cancer. 2006 Feb 15;106(4):759-64. doi: 10.1002/cncr.21655.