murine polyomavirus virus-like particles carrying full-length human psa protect balbc mice from outgrowth of a psa expressing tumor小鼠多瘤病毒病毒样颗粒携带完整的人类psa防止balbc老鼠psa表达肿瘤的产物.pdfVIP

Murine Polyomavirus Virus-Like Particles Carrying Full- Length Human PSA Protect BALB/c Mice from Outgrowth of a PSA Expressing Tumor Mathilda Eriksson*, Kalle Andreasson¤a, Joachim Weidmann, Kajsa Lundberg, Karin Tegerstedt¤b, Tina . ¨ . Dalianis , Torbjorn Ramqvist Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden 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. Citation: Eriksson M, Andreasson K, Weidmann J, Lundberg K, Tegerstedt