NSU-MD Faculty Articles
Title
Enhanced induction of telomerase-specific CD4(+) T cells using dendritic cells transfected with RNA encoding a chimeric gene product.
ISBN or ISSN
0008-5472
Publication Title
Cancer research
Volume
62
Issue
17
Publication Date / Copyright Date
9-1-2002
First Page
5041
Last Page
5048
Publisher
American Association for Cancer Research
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.
Disciplines
Medicine and Health Sciences
Keywords
Antigens, CD, CD4-Positive T-Lymphocytes, Cancer Vaccines, DNA-Binding Proteins, Dendritic Cells, Epitopes, T-Lymphocyte, Humans, Lymphocyte Activation, Lysosome-Associated Membrane Glycoproteins, Membrane Glycoproteins, RNA, Messenger, Recombinant Fusion Proteins, T-Lymphocytes, Cytotoxic, Telomerase, Transfection, Tumor Cells, Cultured
NSUWorks Citation
Su, Zhen; Vieweg, Johannes; Weizer, Alon Z; Dahm, Philipp; Yancey, Donna; Turaga, Vandana; Higgins, John; Boczkowski, David; Gilboa, Eli; and Dannull, Jens, "Enhanced induction of telomerase-specific CD4(+) T cells using dendritic cells transfected with RNA encoding a chimeric gene product." (2002). NSU-MD Faculty Articles. 25.
https://nsuworks.nova.edu/hpd_md_facarticles/25
