Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: In 7 patients, peripheral blood mononuclear cells collected after immunization recognized hTERT:540-548, whereas those collected before vaccination did not. However, none of these CTLs recognized tumors that endogenously expressed telomerase, and none of the patients had an objective clinical response. Several highly avid T-cell clones were generated that recognized T2 cells pulsed with <or=1 nm hTERT:540-548, but none of these recognized HLA-A*0201(+) hTERT(+) tumors or cells transduced with the human telomerase reverse transcriptase (hTERT) gene. Also, an antibody specific for hTERT:540-548/ HLA-A*0201 complexes stained peptide-pulsed cells but not telomerase(+) tumors. CONCLUSIONS: Our results are discordant with previous studies and those of a clinical trial that claimed peripheral blood mononuclear cells from patients vaccinated with peptide-pulsed dendritic cells lysed hTERT(+) tumors. However, our findings are consistent with a previous study that demonstrated that the hTERT:540-548 peptide is cleaved in the proteasome. These results suggest that hTERT:540-548 is not presented on the surfaces of tumor cells in the context of HLA-A*0201 and will not be useful for the immunotherapy of patients with cancer.
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Authors | Maria R Parkhurst, John P Riley, Takehito Igarashi, Yong Li, Paul F Robbins, Steven A Rosenberg |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 10
Issue 14
Pg. 4688-98
(Jul 15 2004)
ISSN: 1078-0432 [Print] United States |
PMID | 15269141
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial)
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Chemical References |
- HLA-A Antigens
- HLA-A*02:01 antigen
- HLA-A2 Antigen
- Peptide Fragments
- RNA, Messenger
- telomerase reverse transcriptase (540-548)
- Telomerase
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Topics |
- Adult
- Aged
- Cell Line
- Cell Line, Tumor
- Enzyme-Linked Immunosorbent Assay
- Female
- Gene Expression
- HLA-A Antigens
(genetics, immunology, metabolism)
- HLA-A2 Antigen
- Humans
- Immunization
- Male
- Middle Aged
- Neoplasm Metastasis
- Neoplasms
(enzymology, immunology, therapy)
- Peptide Fragments
(genetics, immunology, metabolism)
- RNA, Messenger
(genetics, metabolism)
- T-Lymphocytes
(immunology)
- T-Lymphocytes, Cytotoxic
(immunology)
- Telomerase
(genetics, immunology, metabolism)
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