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An anti-nucleic acid antibody delivers antigen to the cross-presentation pathway in dendritic cells and potentiates therapeutic antitumor effects

Authors
Pham, CD; Woo, MY; Kim, YS; Park, S; Kwon, MH
Citation
Journal of immunology (Baltimore, Md. : 1950), 189(12):5755-5763, 2012
Journal Title
Journal of immunology (Baltimore, Md. : 1950)
ISSN
0022-17671550-6606
Abstract
Cross-presentation is important for initiating CTL responses against tumors. Delivery of exogenous Ags to the cross-presentation pathway in dendritic cells (DCs), using a number of different carriers, has been attempted to further understand the mechanisms underlying cross-presentation and to develop therapeutic tumor vaccines. The present study reports a new antigenic carrier molecule: a single-chain V region fragment (scFv) of a nucleic acid-hydrolyzing Ab, 3D8. A fusion protein comprising 3D8 scFv and the CTL epitope OVA(250-264) (chicken OVA aa 250-264) was internalized by DC2.4 DCs and processed via a proteasome-dependent, brefeldin- and cycloheximide-sensitive, chloroquine- and primaquine-insensitive pathway, resulting in loading of the CTL epitope onto H-2K(b). In vivo cross-presentation and cross-priming were efficient, even without adjuvant; injection of mice with 3D8 scFv-OVA(250-264) induced cross-presentation of the CTL epitope by draining lymph node CD11c(+) B7.1(+) MHC class II(high) DCs, elicited a CTL response, and suppressed the growth of tumors expressing the OVA epitope. This report shows that an anti-nucleic acid Ab is used to deliver exogenous Ag to the cross-presentation pathway and inhibit in vivo tumor growth.
MeSH terms
AnimalsAntibodies, Antinuclear/genetics/*metabolismAntigens, Neoplasm/genetics/immunology/*metabolismCell Line, TumorChickensCoculture TechniquesCross-Priming/genetics/*immunologyDendritic Cells/*immunology/metabolism/pathologyEpitopes, T-Lymphocyte/genetics/metabolismMelanoma, Experimental/genetics/*immunology/*therapyMiceMice, Inbred C57BLProtein Transport/immunologyRecombinant Fusion Proteins/genetics/metabolismSingle-Chain Antibodies/*metabolism/therapeutic useTumor Escape/genetics/*immunology
DOI
10.4049/jimmunol.1200804
PMID
23152565
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
박, 선권, 명희
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