Dendritic cells loaded with polyomavirus VP1/VP2Her2 virus-like particles efficiently prevent outgrowth of a Her2/neu expressing tumor

Abstract

One immunization with murine polyomavirus (MPyV) VP1 virus-like particles containing a fusion protein between MPyV VP2 and the extra cellular and transmembrane domain of Her2 (Her2_1–683PyVLPs) efficiently protects BALB/c mice from outgrowth of the Her2 expressing tumor D2F2/E2. To possibly enhance the anti-Her2 immune response and abrogate the induced anti-VLP antibody response, immunization with murine dendritic cells (DCs) loaded with Her2_1–683PyVLPs was performed. Mice were immunized once or more with 5 or 50 μg Her2_1–683PyVLPs alone or loaded on DCs, and challenged 14 days after the last immunization with a lethal dose of Her2-positive D2F2/E2 cells. Mice were protected from tumor outgrowth, when immunized only once with 5 or 50 μg Her2_1–683PyVLPs loaded on DCs, or 50 μg of Her2_1–683PyVLPs alone, whereas immunization once or more with 5 μg of Her2_1–683PyVLPs alone only protected half of the mice. Immunization with recombinant Her2 protein alone, or loaded on DCs, did not induce tumor immunity. Using both immunization strategies, Her2-specific T cell immunity was demonstrated, while Her2-specific antibodies were not detected. Loading VLPs on DCs reduced anti-VLP antibodies sixfold, but did not influence the efficiency of subsequent immunizations. Notably, DC maturation by Her2_1–683PyVLPs in vitro was not demonstrated although the IL-12 production was significantly increased. In conclusion, loading of VLPs on DCs can enhance specific VLP immunization considerably.