|
|
Blood, 15 October 2005, Vol. 106, No. 8, pp. 2663-2670.
Prepublished online as a Blood First Edition Paper on July 7, 2005; DOI 10.1182/blood-2004-09-3742.
 Previous Article | Next Article 
Submitted September 29, 2004
Accepted June 2, 2005
Genomic stability and functional activity may be lost in telomerase transduced human CD8+ T lymphocytes
Marco W Schreurs, Mario A Hermsen, Ramon I Klein Geltink, Kirsten B Scholten, Antoinette A Brink, Esther W Kueter, Marianne Tijssen, Chris J Meijer, Bauke Ylstra, Gerrit A Meijer, and Erik Hooijberg*
Dept. of Pathology, VU University Medical Center (VUMC), Amsterdam, The Netherlands
* Corresponding author; email: erik.hooijberg{at}vumc.nl.
To obtain the large amount of T cells required for adoptive immunotherapy in a clinical setting, T cell life span extension by human telomerase reverse transcriptase (hTERT) transduction is of particular interest. However, constitutive expression of hTERT is associated with malignant transformation and thus warrants a detailed evaluation of the safety of hTERT transduced T cells before clinical application. In view of this, we performed an extensive cytogenetic analysis of hTERT transduced MART-1 and HPV16 E7 specific human CD8+ cytotoxic T lymphocytes (CTL), reactive against melanoma and cervical carcinoma, respectively. Our results, obtained by (spectral) karyotyping and array comparative genomic hybridization, showed the development of minor chromosomal aberrations in an hTERT transduced MART-1 specific CTL clone, whereas severe clonal aberrations were detected in an hTERT transduced HPV16 E7 specific CTL clone. Furthermore, hTERT transduction did not protect CTL from immunosenescence, since the HPV16 E7 specific, hTERT transduced CTL clone showed a decreased functional activity upon prolonged culture. Although the general frequency of major chromosomal aberrations in hTERT transduced CTL and the in vivo significance of our obervations remain still unclear at this point, the currently available data suggest that clinical application of hTERT transduced CTL should proceed with caution.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
H. Vekony, B. Ylstra, S. M. Wilting, G. A. Meijer, M. A. van de Wiel, C. R. Leemans, I. van der Waal, and E. Bloemena
DNA Copy Number Gains at Loci of Growth Factors and Their Receptors in Salivary Gland Adenoid Cystic Carcinoma
Clin. Cancer Res.,
June 1, 2007;
13(11):
3133 - 3139.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Menzel, M. Migliaccio, D. R. Goldstein, S. Dahoun, M. Delorenzi, and N. Rufer
Mechanisms Regulating the Proliferative Potential of Human CD8+ T Lymphocytes Overexpressing Telomerase
J. Immunol.,
September 15, 2006;
177(6):
3657 - 3668.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chen and M. S. Goligorsky
Premature senescence of endothelial cells: Methusaleh's dilemma
Am J Physiol Heart Circ Physiol,
May 1, 2006;
290(5):
H1729 - H1739.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Ylstra, P. van den IJssel, B. Carvalho, R. H. Brakenhoff, and G. A. Meijer
BAC to the future! or oligonucleotides: a perspective for micro array comparative genomic hybridization (array CGH)
Nucleic Acids Res.,
January 26, 2006;
34(2):
445 - 450.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
