Baculovirus activates murine dendritic cells and induces non-specific NK cell and T cell immune responses

Suzuki, Toshiya; Chang, Myint Oo; Kitajima, Masayuki; Takaku, Hiroshi

doi:10.1016/j.cellimm.2009.12.005

Cited by 42 publications

(49 citation statements)

References 35 publications

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“…13 These responses altogether conferred the animals the antitumor immunity as reported previously 41 and as evidenced by the slightly hindered tumor progression (Figures 4a and 6a) by the control virus Bac-SB-T2luc/w. These properties rendered baculovirus a powerful adjuvant to potentiate the antitumor efficacies.…”

Section: Discussionsupporting

confidence: 74%

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

et al. 2011

Gene Ther

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Antiangiogenesis is an appealing anticancer approach but requires continued presence of the antiangiogenic agents, which can be remedied by gene therapy. Baculovirus is an emerging gene delivery vector but only mediates transient expression (o7 days); thus, this study primarily aimed to develop a hybrid baculovirus for sustained antiangiogenic gene expression and cancer therapy. We first constructed plasmids featuring adeno-associated virus inverted terminal repeats (AAV ITRs), oriP/ Epstein-Barr virus-expressed nuclear antigen 1 (EBNA1) or Sleeping Beauty (SB) transposon and compared their efficacies in terms of persistent expression. In human embryonic kidney (HEK293) cells, AAV ITR failed to prolong the expression while oriP/EBNA1 moderately extended the expression to 35 days. In contrast, the SB system led to stable expression beyond 77 days even without antibiotic selection. Given this finding, we constructed a hybrid SB baculovirus expressing the SB transposase and harboring the transgene cassette flanked by inverted repeat/direct-repeat (IR/DR) elements recognizable by SB. The hybrid SB baculovirus efficiently transduced mammalian cells and mediated an expression duration longer than that by conventional baculoviruses, thanks to the transgene persistence and integration. The SB baculovirus (Bac-SB-T2hEA/w) expressing the antiangiogenic fusion protein comprising endostatin and angiostatin (hEA) also enabled prolonged hEA expression. With sustained hEA expression, Bac-SB-T2hEA/w repressed the angiogenesis in vivo, hindered the growth of two different tumors (prostate tumor allografts and human ovarian tumor xenografts) in mice and extended the life span of animals. These data altogether implicated the potential of the hybrid SB-baculovirus vector for prolonged hEA expression and for the treatment of multiple types of angiogenesis-dependent tumors.

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Section: Discussionsupporting

confidence: 74%

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

et al. 2011

Gene Ther

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“…Baculovirus-infected bone marrow-derived dendritic cells (BMDCs) (BV-DCs) showed upregulation of costimulatory molecules, such as CD80, CD86 and MHC classes I and II, and increased secretion of interferons and other proinflammatory cytokines. 22 In this study, we showed that the inoculation of BV-DCs induced efficient CD8 1 T cell-and NK cell-dependent, CD4 1 T cell-independent antitumor immunity. Furthermore, BV-DC administration did not cause any functional damage to the mouse liver or kidneys.…”

Section: Introductionmentioning

confidence: 69%

“…We also showed that BV-DCs upregulated the expression of MHC and costimulatory molecules and increased the secretion of type I interferons and proinflammatory cytokines. 22 Moreover, NK cells or T cells cocultured with BV-DCs produced interferon-c and demonstrated increased cytotoxicity and proliferation. Here, we first evaluated the effects of antitumor immunity against murine lung cancer.…”

Section: Antitumor Effects Of Bv-dcs Against Lung Cancermentioning

confidence: 99%

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Induction of antitumor immunity against mouse carcinoma by baculovirus-infected dendritic cells

et al. 2010

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A dendritic cell (DC) vaccine strategy has been developed as a new cancer immunotherapy, but the goal of complete tumor eradication has not yet been achieved. We have previously shown that baculoviruses potently infect DCs and induce antitumor immunity against hepatomas in a mouse model. Baculovirus-infected, bone marrow-derived DCs (BMDCs) display increased surface expression of costimulatory molecules, such as CD80, CD86 and major histocompatibility complex (MHC) classes I and II, and secrete interferons and other proinflammatory cytokines. In this study, we evaluated the induction of antitumor immunity in mice by baculovirus-infected BMDCs against lung cancer and melanoma. After treatment with baculovirus-infected BMDCs, murine lung tumors caused by Lewis lung carcinoma (LLC) cells were significantly reduced in size, and the survival of the mice was improved. In addition, experiments using a melanoma mouse model showed that baculovirus-infected BMDCs inhibited tumor growth and improved survival compared with controls. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine levels remained normal in baculovirus-infected BMDC-treated mice. Our findings show that baculovirus-infected DCs induce antitumor immunity and pave the way for the use of this technique as an effective tool for DC immunotherapy against malignancies.

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“…The AcMNPV can however transduce mammalian cells, though its replication is restricted to insect cells [3]. Further, due to its high CpG content, baculovirus can stimulate TLR-9 mediated host antiviral innate immune responses [1,17]. Therefore, the baculoviruses are safe to use as vectors for antigen gene delivery.…”

Section: Introductionmentioning

confidence: 99%

Baculovirus mediated transduction: analysis of vesicular stomatitis virus glycoprotein pseudotyping

et al. 2014

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The recombinant baculoviruses were constructed to investigate the necessity of VSV-G pseudotyping for mammalian cell transduction. The viruses were designed to express green fluorescent protein (GFP) gene under the control of cytomegalovirus promoter, with or without pseudotyping with VSV-G. VSV-G was placed under the control of polyhedrin promoter that is recognized by insect cells, allowing the formation of pseudotyped baculovirus. The study findings demonstrate that the pseudotyping of baculovirus significantly enhanced transduction efficiency compared to non-pseudotyped baculovirus, resulting in consequent distinction in the expression of GFP in mammalian cells. The results confirmed that pseudotyping is important for baculovirus mediated gene delivery. Further, when full-length VSV-G pseudotyping was compared with truncated VSV-G containing GED domain (G-stem of ectodomain in conjunction with the TM and CT domains of the glycoprotein), latter was relatively less efficient in transducing mammalian cells. This study demonstrated that pseudotyping with full-length VSV-G had better transduction efficiency in mammalian cells. However, at higher multiplicity of infection, both fulllength and truncated VSV-G showed equivalent transduction. This study established the significance of pseudotyping of baculovirus with full-length VSV-G for efficient transduction of mammalian cells, utilizing the highly sensitive GFP marker system. These findings have significant implications in designing of baculovirus vector based antigen delivery for developing new generation vaccines.

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Baculovirus activates murine dendritic cells and induces non-specific NK cell and T cell immune responses

Cited by 42 publications

References 35 publications

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

Development of the hybrid Sleeping Beauty-baculovirus vector for sustained gene expression and cancer therapy

Induction of antitumor immunity against mouse carcinoma by baculovirus-infected dendritic cells

Baculovirus mediated transduction: analysis of vesicular stomatitis virus glycoprotein pseudotyping

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