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 OVA250–264 (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-2Kb. In vivo cross-presentation and cross-priming were efficient, even without adjuvant; injection of mice with 3D8 scFv-OVA250–264 induced cross-presentation of the CTL epitope by draining lymph node CD11c+ B7.1+ MHC class IIhigh 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.