Telomerase mRNA-Transfected Dendritic Cells Stimulate Antigen-Specific CD8 super(+) and CD4 super(+) T Cell Responses in Patients with Metastatic Prostate Cancer
Telomerase reverse transcriptase (hTERT) represents an attractive target for cancer immunotherapy because hTERT is reactivated in most human tumors. A clinical trial was initiated in which hTERT mRNA-transfected dendritic cells (DC) were administered to 20 patients with metastatic prostate cancer. N...
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Published in | The Journal of immunology (1950) Vol. 174; no. 6; pp. 3798 - 3807 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
15.03.2005
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Online Access | Get full text |
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Summary: | Telomerase reverse transcriptase (hTERT) represents an attractive target for cancer immunotherapy because hTERT is reactivated in most human tumors. A clinical trial was initiated in which hTERT mRNA-transfected dendritic cells (DC) were administered to 20 patients with metastatic prostate cancer. Nine of these subjects received DC transfected with mRNA encoding a chimeric lysosome- associated membrane protein-1 (LAMP) hTERT protein, allowing for concomitant induction of hTERT-specific CD8 super(+) and CD4 super(+) T cell responses. Treatment was well tolerated. Intense infiltrates of hTERT-specific T cells were noted at intradermal injection sites after repeated vaccination. In 19 of 20 subjects, expansion of hTERT-specific CD8 super(+) T cells was measured in the peripheral blood of study subjects, with 0.9-1.8% of CD8 super(+) T cells exhibiting Ag specificity. Patients immunized with the chimeric LAMP hTERT vaccine developed significantly higher frequencies of hTERT-specific CD4 super(+) T cells than subjects receiving DC transfected with the unmodified hTERT template. Moreover, CTL-mediated killing of hTERT targets was enhanced in the LAMP hTERT group, suggesting that an improved CD4 super(+) response could augment a CTL response. Vaccination was further associated with a reduction of prostate-specific Ag velocity and molecular clearance of circulating micrometastases. Our findings provide a rationale for further development of hTERT-transfected DC vaccines in the treatment of prostate and other cancers. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-1 |
ISSN: | 0022-1767 |