title: An anti-nucleic acid antibody delivers antigen to the cross-presentation pathway in dendritic cells and potentiates therapeutic antitumor effects.
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.
authors.affiliation: Department of Microbiology, Ajou University School of Medicine, Suwon 443-749, South Korea.
authors.forename: Chuong D
authors.initials: CD
authors.lastname: Pham
authors.forename: Min-Yeong
authors.initials: MY
authors.lastname: Woo
authors.forename: Yong-Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Sun
authors.initials: S
authors.lastname: Park
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Kwon
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D002645:Chickens; D018920:Coculture Techniques; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D021381:Protein Transport / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000378:metabolism* / Q000627:therapeutic use; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies