Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 2577
© 2005 American Society of Clinical Oncology

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Abstract

Telomerase - a tumor antigen in chronic lymphocytic leukemia (CLL) induces spontaneously autologous leukemia specific cytotoxic T lymphocytes

Karolinska Hosp, Stockholm, Sweden

2577

Background: Human telomerase reverse transcriptase (hTERT) is the catalytic domain of the functional telomerase complex, which expression is absent and/or transient in most normal human adult cells, but high in most tumor cells. Almost 90% of human tumors display high levels of telomerase expression, implying the possibility of using hTERT as a target for cancer immunotherapy. Methods: Peripheral blood mononuclear cells (PBMC) from 26 B-CLL pts were tested for telomerase expression by RT-PCR. Monocyte-derived dendritic cells (DC) were generated from PBMC of 4 telomerase positive and 2 telomerase-negative CLL patients. DC were pulsed with a 16 mer amino acid long peptide from hTERT and with a RAS peptide as control. To assess telomerase-specific T cells, IFN- production (ELISPOT), ³H thymidine incorporation, MHC blocking, and cytotoxicity assays were used. Results: PCR showed that hTERT was expressed in 13 out of 26 pts. Among the 13 telomerase-positive pts, 4 were selected for hTERT-specific CTL expansion. In all 4 pts DC pulsed with hTERT peptide could generate CTL against the autologous leukemic cells upon two rounds of restimulation with a specific lysis of 58±12% (mean± SEM). The corresponding figures for Ras stimulated T cells were15±3.5% lysis (p<0.025). In two telomerase-negative pts telomerase specific CTLs recognizing the autologous leukemic B cells could not be expanded. Telomerase expanded T cells induced 1.8± 0.2% lysis of tumor B cells and the control Ras peptide 1.7 ± 1% lysis. Comparing lytic capacity of telomerase positive and negative pts was statistically significant (p<0.027). In 2 out of 4 pts a proliferative response against hTERT was noted in fresh T cells. No restimulation was done. MHC class I and MHC class II blocking revealed that the proliferative response was both MHC I and MHC II-dependent. No INF- production was detected in fresh isolated T cells stimulated once with the peptide. Conclusion: Our data show that CLL pts with telomerase positive leukemic cells have spontaneously occurring telomerase specific T cells able to lyse the leukemic cells. The results indicate that telomerase might be a valid target structure for vaccine development in CLL.

No significant financial relationships to disclose.

Abstract presentation from the 2005 ASCO Annual Meeting