| Autor: |
Schreurs, Marco W.J., Hermsen, Mario A.J.A., Geltink, Ramon I. Klein, Scholten, Kirsten B.J., Brink, Antoinette A.T.P., Kueter, Esther W.M., Tijssen, Marianne, Meijer, Chris J.L.M., Ylstra, Bauke, Meijer, Gerrit A., Hooijberg, Erik |
| Zdroj: |
Blood; October 2005, Vol. 106 Issue: 8 p2663-2670, 8p |
| Abstrakt: |
To obtain the large amount of T cells required for adoptive immunotherapy in a clinical setting, T-cell lifespan 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 (melanoma antigen recognized by T cell 1)–and human papillomavirus type 16 (HPV16) E7–specific human CD8+cytotoxic T lymphocytes (CTLs), 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 CTLs from immunosenescence, because the HPV16 E7–specific, hTERT-transduced CTL clone showed a decreased functional activity on prolonged culture. Although the general frequency of major chromosomal aberrations in hTERT-transduced CTLs and the in vivo significance of our observations remain still unclear at this point, the currently available data suggest that clinical application of hTERT-transduced CTLs should proceed with caution. |
| Databáze: |
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