Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product

Zhen Su, Johannes Vieweg, Alon Z. Weizer, Philipp Dahm, Donna Yancey, Vandana Turaga, John Higgins, David Boczkowski, Eli Gilboa, Jens Dannull

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Dendritic cells (DCs) transfected with mRNA encoding human telomerase reverse transcriptase (hTERT) have been shown to represent potent inducers of CTLs and antitumor immunity. However, it has become widely accepted that not only CTLs but also CD4+ T helper cells are critical to the generation, as well as to the maintenance, of potent antitumor responses in vivo. In this study, we sought to determine whether human DCs transfected with mRNA encoding a chimeric hTERT/lysosome-associated membrane protein (LAMP-1) protein, carrying the endosomal/lysosomal sorting signal of the LAMP-1, are capable of stimulating concomitant hTERT-specific CD8+ and CD4+ T-cell responses in vitro. We show that processing of hTERT/LAMP-1 transcripts leads to enhanced stimulation of hTERT-specific CD4+ T cells and does not negatively affect intracellular generation and subsequent presentation of MHC class I epitopes, hence, generating a CTL response. These findings provide a preclinical rationale of using DCs transfected with the chimeric hTERT/LAMP-1 RNA in vaccine trials to facilitate generation of antigen-specific CD4+ T-cell responses that may be required to stimulate and maintain an optimal CD8+ CTL response in vivo.

Original languageEnglish
Pages (from-to)5041-5048
Number of pages8
JournalCancer Research
Volume62
Issue number17
StatePublished - Sep 1 2002
Externally publishedYes

Fingerprint

Telomerase
Dendritic Cells
RNA
T-Lymphocytes
Lysosome-Associated Membrane Glycoproteins
Genes
CD4 Antigens
Messenger RNA
Helper-Inducer T-Lymphocytes
human TERT protein
Epitopes
Immunity
Vaccines
Maintenance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Su, Z., Vieweg, J., Weizer, A. Z., Dahm, P., Yancey, D., Turaga, V., ... Dannull, J. (2002). Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product. Cancer Research, 62(17), 5041-5048.

Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product. / Su, Zhen; Vieweg, Johannes; Weizer, Alon Z.; Dahm, Philipp; Yancey, Donna; Turaga, Vandana; Higgins, John; Boczkowski, David; Gilboa, Eli; Dannull, Jens.

In: Cancer Research, Vol. 62, No. 17, 01.09.2002, p. 5041-5048.

Research output: Contribution to journalArticle

Su, Z, Vieweg, J, Weizer, AZ, Dahm, P, Yancey, D, Turaga, V, Higgins, J, Boczkowski, D, Gilboa, E & Dannull, J 2002, 'Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product', Cancer Research, vol. 62, no. 17, pp. 5041-5048.
Su, Zhen ; Vieweg, Johannes ; Weizer, Alon Z. ; Dahm, Philipp ; Yancey, Donna ; Turaga, Vandana ; Higgins, John ; Boczkowski, David ; Gilboa, Eli ; Dannull, Jens. / Enhanced induction of telomerase-specific CD4+ T cells using dendritic cells transfected with RNA encoding a chimeric gene product. In: Cancer Research. 2002 ; Vol. 62, No. 17. pp. 5041-5048.
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