NSU-MD Faculty Articles
Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer.
Publication Title
Journal of immunology
Publisher
American Association of Immunologists
ISSN
0022-1767
Publication Date
3-15-2005
Keywords
Aged, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cancer Vaccines, DNA-Binding Proteins, Dendritic Cells, Humans, Immunotherapy, Male, Middle Aged, Prostatic Neoplasms, RNA, Messenger, Safety, Telomerase, Transfection
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.
Volume
174
Issue
6
First Page
3798
Last Page
3807
Disciplines
Medicine and Health Sciences
NSUWorks Citation
Su, Zhen; Dannull, Jens; Yang, Benjamin K; Dahm, Philipp; Coleman, Doris; Yancey, Donna; Sichi, Sylvia; Niedzwiecki, Donna; Boczkowski, David; Gilboa, Eli; and Vieweg, Johannes, "Telomerase mRNA-transfected dendritic cells stimulate antigen-specific CD8+ and CD4+ T cell responses in patients with metastatic prostate cancer." (2005). NSU-MD Faculty Articles. 35.
https://nsuworks.nova.edu/hpd_md_facarticles/35
