title: Murine polyomavirus virus-like particles carrying full-length human PSA protect BALB/c mice from outgrowth of a PSA expressing tumor.
abstract: Virus-like particles (VLPs) consist of capsid proteins from viruses and have been shown to be usable as carriers of protein and peptide antigens for immune therapy. In this study, we have produced and assayed murine polyomavirus (MPyV) VLPs carrying the entire human Prostate Specific Antigen (PSA) (PSA-MPyVLPs) for their potential use for immune therapy in a mouse model system. BALB/c mice immunized with PSA-MPyVLPs were only marginally protected against outgrowth of a PSA-expressing tumor. To improve protection, PSA-MPyVLPs were co-injected with adjuvant CpG, either alone or loaded onto murine dendritic cells (DCs). Immunization with PSA-MPyVLPs loaded onto DCs in the presence of CpG was shown to efficiently protect mice from tumor outgrowth. In addition, cellular and humoral immune responses after immunization were examined. PSA-specific CD4(+) and CD8(+) cells were demonstrated, but no PSA-specific IgG antibodies. Vaccination with DCs loaded with PSA-MPyVLPs induced an eight-fold lower titre of anti-VLP antibodies than vaccination with PSA-MPyVLPs alone. In conclusion, immunization of BALB/c mice with PSA-MPyVLPs, loaded onto DCs and co-injected with CpG, induces an efficient PSA-specific tumor protective immune response, including both CD4(+) and CD8(+) cells with a low induction of anti-VLP antibodies.
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Mathilda.Eriksson@ki.se
authors.forename: Mathilda
authors.initials: M
authors.lastname: Eriksson
authors.forename: Kalle
authors.initials: K
authors.lastname: Andreasson
authors.forename: Joachim
authors.initials: J
authors.lastname: Weidmann
authors.forename: Kajsa
authors.initials: K
authors.lastname: Lundberg
authors.forename: Karin
authors.initials: K
authors.lastname: Tegerstedt
authors.forename: Tina
authors.initials: T
authors.lastname: Dalianis
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Ramqvist
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D011120:Polyomavirus / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D047368:Tumor Burden / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019496:Cancer Vaccines; D036022:Capsid Proteins; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D058425:Vaccines, Virus-Like Particle; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen