Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity

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

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) exhibit potent immunostimulating activity by binding with Toll-like receptor 9 (TLR9) expressed on antigen-presenting cells. Here, we show that CpG-ODN encapsulated in cationic liposomes (CpG-liposomes) improves its incorporation into CD11c+ dendritic cells (DCs) and induces enhanced serum interleukin (IL)-12 levels compared with unmodified CpG-ODN. CpG-liposome potently activated natural killer (NK) cells (84.3%) and NKT cells (48.3%) to produce interferon-γ (IFN-γ), whereas the same dose of unmodified CpG-ODN induced only low numbers of IFN-γ-producing NK cells (12.7%) and NKT cells (1.6%) to produce IFN-γ. In contrast with the NKT cell agonist α-galactosylceramide, which induces both IFN-γ and IL-4 production by NKT cells, CpG-liposome only induced IFN-γ production by NKT cells. Such potent adjuvant activities of CpG-liposome were absent in TLR9-deficient mice, indicating that CpG-liposome was as effective as CpG-ODN in stimulating type 1 innate immunity through TLR9. In addition to TLR9, at least two other factors, IL-12 production by DCs and direct contact between DCs and NK or NKT cells, were essential for inducing type 1 innate immunity by CpG-liposome. Furthermore, ligation of TLR9 by CpG-liposome co-encapsulated with ovalbumin (OVA) caused the induction of OVA-specific CTLs, which exhibited potent cytotoxicity against OVA-expressing tumor cells. These results indicate that CpG-liposome alone or combined with tumor antigen protein provides a promising approach for the prevention or therapy of tumors.

Original languageEnglish (US)
Pages (from-to)8754-8760
Number of pages7
JournalCancer Research
Volume64
Issue number23
DOIs
StatePublished - Dec 1 2004

Fingerprint

Oligodeoxyribonucleotides
Innate Immunity
Liposomes
Natural Killer T-Cells
Toll-Like Receptor 9
Cytosine
Guanine
Interferons
Ovalbumin
Natural Killer Cells
Dendritic Cells
Interleukin-12
Galactosylceramides
Neoplasm Antigens
Antigen-Presenting Cells
Interleukin-4
Ligation
Neoplasms
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Suzuki, Y., Wakita, D., Chamoto, K., Narita, Y., Tsuji, T., Takeshima, T., ... Nishimura, T. (2004). Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity. Cancer Research, 64(23), 8754-8760. https://doi.org/10.1158/0008-5472.CAN-04-1691

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, You; Kondo, Satoshi; Akira, Shizuo; Katoh, Hiroyuki; Ikeda, Hiroaki; Nishimura, Takashi.

In: Cancer Research, Vol. 64, No. 23, 01.12.2004, p. 8754-8760.

Research output: Contribution to journalArticle

Suzuki, Y, Wakita, D, Chamoto, K, Narita, Y, Tsuji, T, Takeshima, T, Gyobu, H, Kawarada, Y, Kondo, S, Akira, S, Katoh, H, Ikeda, H & Nishimura, T 2004, 'Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity', Cancer Research, vol. 64, no. 23, pp. 8754-8760. https://doi.org/10.1158/0008-5472.CAN-04-1691
Suzuki, Yoshinori ; Wakita, Daiko ; Chamoto, Kenji ; Narita, Yoshinori ; Tsuji, Takemasa ; Takeshima, Tsuguhide ; Gyobu, Hiroshi ; Kawarada, You ; Kondo, Satoshi ; Akira, Shizuo ; Katoh, Hiroyuki ; Ikeda, Hiroaki ; Nishimura, Takashi. / Liposome-encapsulated CpG oligodeoxynucleotides as a potent adjuvant for inducing type 1 innate immunity. In: Cancer Research. 2004 ; Vol. 64, No. 23. pp. 8754-8760.
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abstract = "Unmethylated cytosine-phosphorothioate-guanine oligodeoxynucleotides (CpG-ODNs) exhibit potent immunostimulating activity by binding with Toll-like receptor 9 (TLR9) expressed on antigen-presenting cells. Here, we show that CpG-ODN encapsulated in cationic liposomes (CpG-liposomes) improves its incorporation into CD11c+ dendritic cells (DCs) and induces enhanced serum interleukin (IL)-12 levels compared with unmodified CpG-ODN. CpG-liposome potently activated natural killer (NK) cells (84.3{\%}) and NKT cells (48.3{\%}) to produce interferon-γ (IFN-γ), whereas the same dose of unmodified CpG-ODN induced only low numbers of IFN-γ-producing NK cells (12.7{\%}) and NKT cells (1.6{\%}) to produce IFN-γ. In contrast with the NKT cell agonist α-galactosylceramide, which induces both IFN-γ and IL-4 production by NKT cells, CpG-liposome only induced IFN-γ production by NKT cells. Such potent adjuvant activities of CpG-liposome were absent in TLR9-deficient mice, indicating that CpG-liposome was as effective as CpG-ODN in stimulating type 1 innate immunity through TLR9. In addition to TLR9, at least two other factors, IL-12 production by DCs and direct contact between DCs and NK or NKT cells, were essential for inducing type 1 innate immunity by CpG-liposome. Furthermore, ligation of TLR9 by CpG-liposome co-encapsulated with ovalbumin (OVA) caused the induction of OVA-specific CTLs, which exhibited potent cytotoxicity against OVA-expressing tumor cells. These results indicate that CpG-liposome alone or combined with tumor antigen protein provides a promising approach for the prevention or therapy of tumors.",
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AU - Suzuki, Yoshinori

AU - Wakita, Daiko

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AU - Narita, Yoshinori

AU - Tsuji, Takemasa

AU - Takeshima, Tsuguhide

AU - Gyobu, Hiroshi

AU - Kawarada, You

AU - Kondo, Satoshi

AU - Akira, Shizuo

AU - Katoh, Hiroyuki

AU - Ikeda, Hiroaki

AU - Nishimura, Takashi

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