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Enhancement of dendritic cell-based vaccine potency by targeting antigen to endosomal/lysosomal compartments

Authors
Kang, Tae HeungLee, Jin HyupBae, Hyun CheolNoh, Kyung HeeKim, Jin HeeSong, Chung KilShin, Byung ChulHung, Chien-FuWu, T. -C.Park, Jong-SupKim, Tae Woo
Issue Date
Aug-2006
Publisher
ELSEVIER SCIENCE BV
Keywords
dendritic cell; lysosome; human papillomavirus (HPV); immunotherapy
Citation
IMMUNOLOGY LETTERS, v.106, no.2, pp 126 - 134
Pages
9
Journal Title
IMMUNOLOGY LETTERS
Volume
106
Number
2
Start Page
126
End Page
134
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/15080
DOI
10.1016/j.imlet.2006.05.004
ISSN
0165-2478
1879-0542
Abstract
Dendritic cells (DCs) are the central players in cancer immunotherapy because of their distinct ability to prime immune responses. In previous work with DNA vaccines, we described an intracellular targeting approach that routed a nuclear/cytoplasmic antigen, human papillomavirus (HPV) type 16 E7, into the endosomal and lysosomal compartments. It does so by linking E7 with the sorting signal of lysosome-associated membrane protein 1 (Sig/LAMP-1) to enhance the presentation of E7 antigen to MHC class I-restricted CD8(+) T cells, as well as to MHC class II-restricted CD4(+) T cells. To date, the Sig/LAMP-1 targeting strategy has not been tested in the context of DC-based vaccines. This study was designed to determine whether targeting HPV-16 E7 to the endosomal/lysosomal compartment can enhance the potency of DC vaccines. In immunological studies, DC-Sig/E7/LAMP-1 dramatically increased in vitro activation and in vivo expansion of E7-specific CD4(+) and CD8(+) T cells, compared with DC-E7 and DC-No insert. More importantly, in both tumor prevention and tumor treatment assays, DC-Sig/E7/LAMP-1 generated greater anti-tumor immunity against TC-1 than DC-ET Our results demonstrate that linkage of the antigen gene to an endosomal/lysosomal targeting signal may greatly enhance the potency of DC-based vaccines. (c) 2006 Elsevier B.V. All rights reserved.
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