PMID- 15958591
OWN - NLM
STAT- MEDLINE
DCOM- 20050808
LR  - 20111117
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 65
IP  - 12
DP  - 2005 Jun 15
TI  - Artificial antigen-presenting cells transduced with telomerase efficiently expand 
      epitope-specific, human leukocyte antigen-restricted cytotoxic T cells.
PG  - 5417-27
AB  - Human telomerase reverse transcriptase (hTERT) is overexpressed in most human 
      tumors, making it a potential target for cancer immunotherapy. hTERT-derived CTL 
      epitopes have been identified previously, including p865 (RLVDDFLLV) and p540 
      (ILAKFLHWL), which are restricted by the human leukocyte antigen (HLA) class I 
      A*0201 allele. However, it remains a major challenge to efficiently and 
      consistently expand hTERT-specific CTLs from donor peripheral blood T 
      lymphocytes. To bypass the need for generating conventional antigen-presenting 
      cells (APC) on an autologous basis, we investigated the potential ability of 
      fibroblast-derived artificial APCs (AAPC) to activate and expand 
      HLA-A*0201-restricted CTLs. We show here that AAPCs stably expressing HLA-A*0201, 
      human beta(2)-microglobulin, B7.1, intercellular adhesion molecule-1, and LFA-3, 
      together with either p540 and p865 minigenes or the full-length hTERT, 
      effectively stimulate tumoricidal, hTERT-specific CTLs. hTERT-expressing AAPCs 
      stimulated both p540 and p865 CTLs as shown by peptide-specific cytolysis and 
      tetramer staining, indicating that hTERT is processed by the AAPCs and that the 
      two peptides are presented as codominant epitopes. The level of cytotoxic 
      activity against a panel of tumors comprising hematologic and epithelial 
      malignancies varied, correlating overall with the level of HLA-A2 and hTERT 
      expression by the target cell. Starting from 100 mL blood, approximately 100 
      million hTERT-specific CTLs could be generated over the course of five sequential 
      stimulations, representing an expansion of approximately 1 x 10(5). Our data show 
      that AAPCs process hTERT antigen and efficiently stimulate hTERT-specific CTLs 
      from human peripheral blood T lymphocytes and suggest that sufficient expansion 
      could be achieved to be clinically useful for adoptive cell therapy.
FAU - Dupont, Jakob
AU  - Dupont J
AD  - Department of Medicine, Memorial Sloan-Kettering Cancer Center and the Joan and 
      Sanford Weill Medical College of Cornell University and Immunology Program, 
      Sloan-Kettering Institute, New York, New York 10021, USA. gynbreast@mskcc.org
FAU - Latouche, Jean-Baptiste
AU  - Latouche JB
FAU - Ma, Chia
AU  - Ma C
FAU - Sadelain, Michel
AU  - Sadelain M
LA  - eng
GR  - CA-23766/CA/NCI NIH HHS/United States
GR  - CA-59350/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Peptide Fragments)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antigen-Presenting Cells/*immunology
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins
MH  - Epitopes, T-Lymphocyte/biosynthesis/genetics/*immunology
MH  - HLA-A Antigens/genetics/immunology
MH  - HLA-A2 Antigen
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - K562 Cells
MH  - Lymphocyte Activation
MH  - Mice
MH  - Molecular Sequence Data
MH  - Peptide Fragments/genetics/immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Telomerase/genetics/*immunology/metabolism
MH  - Transduction, Genetic
MH  - Transfection
EDAT- 2005/06/17 09:00
MHDA- 2005/08/09 09:00
CRDT- 2005/06/17 09:00
PHST- 2005/06/17 09:00 [pubmed]
PHST- 2005/08/09 09:00 [medline]
PHST- 2005/06/17 09:00 [entrez]
AID - 65/12/5417 [pii]
AID - 10.1158/0008-5472.CAN-04-2991 [doi]
PST - ppublish
SO  - Cancer Res. 2005 Jun 15;65(12):5417-27. doi: 10.1158/0008-5472.CAN-04-2991.