Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer

Zhen Su, Jens Dannull, Benjamin K. Yang, Philipp Dahm, Doris Coleman, Donna Yancey, Sylvia Sichi, Donna Niedzwiecki, David Boczkowski, Eli Gilboa, Johannes Vieweg

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279 Scopus citations

Abstract

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+ and CD4+ 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+ T cells was measured in the peripheral blood of study subjects, with 0.9-1.8% of CD8+ T cells exhibiting Ag specificity. Patients immunized with the chimeric LAMP hTERT vaccine developed significantly higher frequencies of hTERT-specific CD4+ 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+ 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.

Original languageEnglish (US)
Pages (from-to)3798-3807
Number of pages10
JournalJournal of Immunology
Volume174
Issue number6
DOIs
StatePublished - Mar 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Su, Z., Dannull, J., Yang, B. K., Dahm, P., Coleman, D., Yancey, D., Sichi, S., Niedzwiecki, D., Boczkowski, D., Gilboa, E., & Vieweg, J. (2005). Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer. Journal of Immunology, 174(6), 3798-3807. https://doi.org/10.4049/jimmunol.174.6.3798