Dendritic cells loaded with polyomavirus VP1/VP2Her2 virus-like particles efficiently prevent outgrowth of a Her2/neu expressing tumor.
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(1-683)PyVLPs) 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(1-683)PyVLPs was performed. Mice were immunized once or more with 5 or 50 microg Her2(1-683)PyVLPs 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 mug Her2(1-683)PyVLPs loaded on DCs, or 50 mug of Her2(1-683)PyVLPs alone, whereas immunization once or more with 5 mug of Her2(1-683)PyVLPs 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(1-683)PyVLPs 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.
Tegerstedt
Karin
K
Department of Oncology-Pathology, Karolinska Institute, Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden. Karin.Tegerstedt@ki.se
Franzén
Andrea
A
Ramqvist
Torbjörn
T
Dalianis
Tina
T
D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
D019496:Cancer Vaccines; D036022:Capsid Proteins; D018664:Interleukin-12; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins; C062481:VP1 protein, polyomavirus; C442543:VP2 protein, Polyomavirus