Liposome-Encapsulated CpG Oligodeoxynucleotides as a Potent Adjuvant for Inducing Type 1 Innate Immunity

Suzuki, Yoshinori; Wakita, Daiko; Chamoto, Kenji; Narita, Yoshinori; Tsuji, Takemasa; Takeshima, Tsuguhide; Gyobu, Hiroshi; Kawarada, Yo; Kondo, Satoshi; Akira, Shizuo; Katoh, Hiroyuki; Ikeda, Hiroaki; Nishimura, Takashi

doi:10.1158/0008-5472.can-04-1691

Cited by 112 publications

(97 citation statements)

References 60 publications

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“…Two months later, mice that survived the first tumor rechallenge received a second rechallenge with 5 Â 10 4 B16OVA or B16F10 cells. Mice were sacrificed when tumor volume exceeded 1,500 mm 3 .…”

Section: Methodsmentioning

confidence: 99%

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In vivo Colocalization of Antigen and CpG within Dendritic Cells Is Associated with the Efficacy of Cancer Immunotherapy

Nierkens¹,

Brok²,

Sutmuller³

et al. 2008

Cancer Research

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Immunostimulatory cytidyl guanosyl (CpG) motifs are of great interest as cancer vaccine adjuvants. They act as potent inducers of Th1 responses, including the activation of cytotoxic CD8 + T lymphocytes (CTL). Whereas animal models have provided clear evidence that CpG enhances antitumor immunity, clinical trials in humans have thus far been less successful. Applying cryosurgery as an instant in situ tumor destruction technique, we now show that timing of CpG administration crucially affects colocalization of antigen and CpG within EEA-1 + and LAMP-1 + compartments within dendritic cells in vivo. Moreover, antigen/CpG colocalization is directly correlated with antigen cross-presentation, the presence of CTL, and protective antitumor immunity. Thus, failure or success of CpG as a vaccine adjuvant may depend on colocalization of antigen/CpG inside DCs and hence on the timing of CpG administration. These data might aid in the design of future immunotherapeutic strategies for cancer patients. [Cancer Res 2008;68(13):5390-6]

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Section: Methodsmentioning

confidence: 99%

“…[2][3][4]. TLR9 is predominantly expressed by B cells and dendritic cells (DC) that internalize and directly respond to CpG (5).…”

Section: Introductionmentioning

confidence: 99%

In vivo Colocalization of Antigen and CpG within Dendritic Cells Is Associated with the Efficacy of Cancer Immunotherapy

Nierkens¹,

Brok²,

Sutmuller³

et al. 2008

Cancer Research

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“…TLR9 recognizes as ligands viral and bacterial CpG-DNA motifs, which when bound to TLR9 on macrophages and DC, causes their activation [38][39][40]. A number of studies indicate that CpG-DNA TLR9 interaction can drive a Th1 immune response, as evidenced by a Th1-dominated cytokine profile [41][42][43]. A recent report demonstrated that TLR9 played an important role in the regulation of the mycobacteriainduced Th1 responses during M. tuberculosis infection in vivo [44].…”

Section: Introductionmentioning

confidence: 99%

TLR9 activation is a key event for the maintenance of a mycobacterial antigen‐elicited pulmonary granulomatous response

et al. 2007

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Type 1 (Th1) granulomas can be studied in mice sensitized with mycobacterium antigens followed by challenge of agarose beads covalently coupled to purified protein derivative. TLR9 is known to play a role in the regulation of Th1 responses; thus, we investigated the role of TLR9 in granuloma formation during challenge with mycobacterium antigens and demonstrated that mice deficient in TLR9 had increased granuloma formation, but a dramatically altered cytokine phenotype. Th1 cytokine levels of IFN-c and IL-12 in the lungs were decreased in TLR9 -/-mice when compared to wild-type mice. In contrast, Th2 cytokine levels of IL-4, IL-5, and IL-13 were increased in TLR9 -/-mice. The migration of CD4 + T cells in the granuloma was impaired, while the number of F4/80 + macrophages was increased in TLR9 -/-mice. Macrophages in the lungs of the TLR9-deficient animals with developing granulomas expressed significantly lower levels of the classically activated macrophage marker, nitric oxide synthase, but higher levels of the alternatively activated macrophage markers such as 'found in inflammatory zone-1 0 antigen and Arginase-1. These results suggest that TLR9 plays an important role in maintaining the appropriate phenotype in a Th1 granulomatous response.

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“…In addition, IL-12 and TNF- synergistically induces IFN- positive CTL and effective antitumor activity [34]. Moreover, IL-12 and TNF- also activate NK, NKT and Th1 cells, which also play an important role in tumor rejection [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Extracts of Larix Leptolepis effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner

Koizumi

Masuko

Wakita

et al. 2012

Cellular Immunology

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Liposome-Encapsulated CpG Oligodeoxynucleotides as a Potent Adjuvant for Inducing Type 1 Innate Immunity

Abstract: ABSTRACT

Cited by 112 publications

References 60 publications

In vivo Colocalization of Antigen and CpG within Dendritic Cells Is Associated with the Efficacy of Cancer Immunotherapy

In vivo Colocalization of Antigen and CpG within Dendritic Cells Is Associated with the Efficacy of Cancer Immunotherapy

TLR9 activation is a key event for the maintenance of a mycobacterial antigen‐elicited pulmonary granulomatous response

Extracts of Larix Leptolepis effectively augments the generation of tumor antigen-specific cytotoxic T lymphocytes via activation of dendritic cells in TLR-2 and TLR-4-dependent manner

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