PMID- 18288212
OWN - NLM
STAT- MEDLINE
DCOM- 20080611
LR  - 20121115
IS  - 1476-5462 (Electronic)
IS  - 0969-7128 (Linking)
VI  - 15
IP  - 9
DP  - 2008 May
TI  - Long-term phenotypic, functional and genetic stability of cancer-specific T-cell 
      receptor (TCR) alphabeta genes transduced to CD8+ T cells.
PG  - 695-9
LID - 10.1038/sj.gt.3303099 [doi]
AB  - In adoptive T-cell transfer as an intervention for malignant diseases, retroviral 
      transfer of T-cell receptor (TCR) genes derived from CD8(+) cytotoxic 
      T-lymphocyte (CTL) clones provides an opportunity to generate a large number of T 
      cells with the same antigen specificity. We cloned the TCR-alphabeta genes from a 
      human leukocyte antigen (HLA)-A(*)2402-restricted CTL clone specific for 
      MAGE-A4(143-151). The TCR-alphabeta genes were transduced to 99.2% of non-TCR 
      expressing SupT1, a human T-cell line, and to 12.7-32.6% of polyclonally 
      activated CD8(+) T cells by retroviral transduction. As expected, TCR-alphabeta 
      gene-modified CD8(+) T cells showed cytotoxic activity and interferon-gamma 
      production in response to peptide-loaded T2-A(*)2402 and tumor cell lines 
      expressing both MAGE-A4 and HLA-A(*)2402. A total of 24 clones were established 
      from TCR-alphabeta gene-transduced peripheral blood mononuclear cells and all 
      clones were functional on a transduced TCR-dependent manner. Four clones were 
      kept in culture over 6 months for analyses in detail. The transduced 
      TCR-alphabeta genes were stably maintained phenotypically, functionally and 
      genetically. Our results indicate that TCR-transduced alphabeta T cells by 
      retroviral transduction represent an efficient and promising strategy for 
      adoptive T-cell transfer for long term.
FAU - Hiasa, A
AU  - Hiasa A
AD  - Department of Immuno-Gene Therapy, Mie University Graduate School of Medicine, 
      Mie, Japan.
FAU - Hirayama, M
AU  - Hirayama M
FAU - Nishikawa, H
AU  - Nishikawa H
FAU - Kitano, S
AU  - Kitano S
FAU - Nukaya, I
AU  - Nukaya I
FAU - Yu, S S
AU  - Yu SS
FAU - Mineno, J
AU  - Mineno J
FAU - Kato, I
AU  - Kato I
FAU - Shiku, H
AU  - Shiku H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080221
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adoptive Transfer/*methods
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Cloning, Molecular
MH  - Cytotoxicity Tests, Immunologic
MH  - *Genes, T-Cell Receptor alpha
MH  - *Genes, T-Cell Receptor beta
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Immunophenotyping
MH  - Interferon-gamma/immunology
MH  - Lymphocyte Activation
MH  - Melanoma/immunology/therapy
MH  - Retroviridae/genetics
MH  - T-Cell Antigen Receptor Specificity
MH  - Time
MH  - Transduction, Genetic/*methods
EDAT- 2008/02/22 09:00
MHDA- 2008/06/12 09:00
CRDT- 2008/02/22 09:00
PHST- 2008/02/22 09:00 [pubmed]
PHST- 2008/06/12 09:00 [medline]
PHST- 2008/02/22 09:00 [entrez]
AID - 3303099 [pii]
AID - 10.1038/sj.gt.3303099 [doi]
PST - ppublish
SO  - Gene Ther. 2008 May;15(9):695-9. doi: 10.1038/sj.gt.3303099. Epub 2008 Feb 21.