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

Abstract

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.

Development of hybrid baculovirus vectors for artificial MicroRNA delivery and prolonged gene suppression

“…Finally, recombinant baculovirus can be readily constructed and propagated to high titers in biosafety level 1 facilities by infecting its natural host insect cells . These attributes have prompted researchers to employ baculovirus for a plethora of applications, ranging from protein production (Liu et al, 2010), virus vector production (Huang et al, 2007;Lesch et al, 2008Lesch et al, , 2011, surface display of proteins (Grabherr and Ernst, 2010), delivery of vaccine immunogens Madhan et al, 2010), cancer therapy (Suzuki et al, 2010;Wang and Balasundaram, 2010), cell-based assay development (Kost et al, 2010) to tissue regeneration (Chen et al, 2008;Chuang et al, 2007;Lin et al, 2010). One disadvantage of baculovirus, however, is that it only mediates transient expression, thus impeding its application in complications requiring long-term transgene expression.…”

Local Immune Stimulation by Intravesical Instillation of Baculovirus to Enable Bladder Cancer Therapy

“…Further studies from the same laboratory indicate that baculovirus-induced antitumor action possibly also involves acquired immunity by enhancing tumor-specific cytotoxic T lymphocyte (CTL) responses and tumor-specific antibody production3139. These findings highlight that the intrinsic immunostimulatory property of baculovirus can possibly be favorably exploited for cancer immunotherapy.…”

Baculovirus vectors for antiangiogenesis-based cancer gene therapy

“…Such baculovirus-induced antitumor effects can be at least partly explained by the baculovirus activation of dendritic cells and natural killer cells, 33 which inhibit the tumors in a transgene-independent manner. 34 Consequently, baculovirus has been exploited to treat cancers in liver, 33 skin, 34 lung 34 and brain. 18 This study adds a new dimension to the applications of baculovirus vectors to prostate cancer treatment.…”