Enhanced tumor-specific long-term immunity of hemagglutinating [correction of hemaggluttinating] virus of Japan-mediated dendritic cell-tumor fused cell vaccination by coadministration with CpG oligodeoxynucleotides.
Immunization with dendritic cells (DCs) using various Ag-loading approaches has shown promising results in tumor-specific immunotherapy and immunoprevention. Fused cells (FCs) that are generated from DCs and tumor cells are one of effective cancer vaccines because both known and unknown tumor Ags are presented on the FCs and recognized by T cells. In this study, we attempted to augment antitumor immunity by the combination of DC-tumor FC vaccination with immunostimulatory oligodeoxynucleotides containing CpG motif (CpG ODN). Murine DCs were fused with syngeneic tumor cells ex vivo using inactivated hemagglutinating virus of Japan (Sendai virus). Mice were intradermally (i.d.) immunized with FCs and/or CpG ODN. Coadministration of CpG ODN enhanced the phenotypical maturation of FCs and unfused DCs, and the production of Th1 cytokines, such as IFN-gamma and IL-12, leading to the induction of tumor-specific CTLs without falling into T cell anergy. In addition, immunization with FCs + CpG ODN provided significant protection against lethal s.c. tumor challenge and spontaneous lung metastasis compared with that with either FCs or CpG ODN alone. Furthermore, among mice that rejected tumor challenge, the mice immunized with FCs + CpG ODN, but not the mice immunized with FCs or CpG ODN alone, completely rejected tumor rechallenge, indicating that CpG ODN provided long-term maintenance of tumor-specific immunity induced by FCs. Thus, the combination of DC-tumor FCs and CpG ODN is an effective and feasible cancer vaccine to prevent the generation and recurrence of cancers.
Hiraoka
Kazuya
K
Division of Gene Therapy Science, Department of Geriatric Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
Yamamoto
Seiji
S
Otsuru
Satoru
S
Nakai
Seiji
S
Tamai
Katsuto
K
Morishita
Ryuichi
R
Ogihara
Toshio
T
Kaneda
Yasufumi
Y
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000276:immunology; D002459:Cell Fusion / Q000379:methods; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D006084:Graft Rejection / Q000276:immunology; D016130:Immunophenotyping; D007271:Injections, Intradermal; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary; D008297:Male; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D029082:Sendai virus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D019496:Cancer Vaccines; D016207:Cytokines; D009838:Oligodeoxyribonucleotides; D017778:Vaccines, Combined; D019444:Vaccines, DNA