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Aptamer-targeted antigen delivery

Authors
 Brian C Wengerter  ;  Joseph A Katakowski  ;  Jacob M Rosenberg  ;  Chae Gyu Park  ;  Steven C Almo  ;  Deborah Palliser  ;  Matthew Levy 
Citation
 MOLECULAR THERAPY, Vol.22(7) : 1375-1387, 2014 
Journal Title
 MOLECULAR THERAPY 
ISSN
 1525-0016 
Issue Date
2014
MeSH
Animals ; Antigen Presentation/immunology* ; Antigens/administration & dosage ; Antigens/immunology* ; Aptamers, Nucleotide/administration & dosage* ; Aptamers, Nucleotide/genetics* ; CD8-Positive T-Lymphocytes/immunology ; CHO Cells ; Cricetinae ; Cricetulus ; Dendritic Cells/metabolism ; Immunity, Cellular ; Interferon-gamma/metabolism ; Mice ; Mice, Inbred C57BL
Abstract
Effective therapeutic vaccines often require activation of T cell-mediated immunity. Robust T cell activation, including CD8 T cell responses, can be achieved using antibodies or antibody fragments to direct antigens of interest to professional antigen presenting cells. This approach represents an important advance in enhancing vaccine efficacy. Nucleic acid aptamers present a promising alternative to protein-based targeting approaches. We have selected aptamers that specifically bind the murine receptor, DEC205, a C-type lectin expressed predominantly on the surface of CD8α+ dendritic cells (DCs) that has been shown to be efficient at facilitating antigen crosspresentation and subsequent CD8+ T cell activation. Using a minimized aptamer conjugated to the model antigen ovalbumin (OVA), DEC205-targeted antigen crosspresentation was verified in vitro and in vivo by proliferation and cytokine production by primary murine CD8+ T cells expressing a T cell receptor specific for the major histocompatibility complex (MHC) I-restricted OVA257–264 peptide SIINFEKL. Compared with a nonspecific ribonucleic acid (RNA) of similar length, DEC205 aptamer-OVA-mediated antigen delivery stimulated strong proliferation and production of interferon (IFN)-γ and interleukin (IL)-2. The immune responses elicited by aptamer-OVA conjugates were sufficient to inhibit the growth of established OVA-expressing B16 tumor cells. Our results demonstrate a new application of aptamer technology for the development of effective T cell-mediated vaccines.
Files in This Item:
T201403007.pdf Download
DOI
10.1038/mt.2014.51
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99665
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