Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent.

Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Research Abstract Details 

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Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Abstract Text:

OK-432 is a Streptococcus-derived immunotherapeutic agent for malignancies. Our group has tried to identify the effective components of OK-432 and has succeeded in isolating a lipoteichoic acid-related preparation designated as OK-PSA, which is a strong inducer of T helper 1 (T(H)1) cells, and elicits an anticancer effect via Toll-like receptor (TLR) 4. Conversely, bacterial DNA with unmethylated CpG motifs can stimulate a T(H)1-type host response via TLR9. The unmethylated CpG DNA contained in OK-432 may play a role in its anticancer effect. In the current study, we investigated the effect of OK-432-derived DNA (OK-DNA) in augmenting the anticancer immune response. Analysis of OK-DNA with the restriction enzymes Hpa II and MspI revealed that OK-DNA contained unmethylated CpG motifs. OK-DNA induced TH1-type cytokines such as interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-12, and IL-18 and augmented killer cell activities in vitro on human peripheral blood mononuclear cells, whereas the methylated OK-DNA did not. Cytokines were also produced by OK-DNA-stimulated splenocytes derived from wild-type mice but not from TLR9-deficient mice. In the in vivo study, peritumoral administration of OK-DNA resulted in a significant inhibition of tumor growth in syngeneic tumor-bearing wild-type and TLR4-deficient mice but not in TLR9-deficient mice. The antitumor effect of OK-432 in TLR9-deficient mice was significantly but partially reduced compared with that in wild-type mice, whereas the effect of OK-432 was almost completely eliminated in TLR4-deficient mice. These findings suggest that unmethylated CpG DNA in OK-432 functions as an active component in OK-432-induced anticancer immunity via TLR9.

Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Publishing Authors By Initials

For similar proteins: dna-binding proteins: toll-like receptor 9 research abstracts see: proteins: dna-binding proteins: toll-like receptor 9 research

PUBMED ID PMID:

MEDLINE DATE: 2006 Mar-Apr

Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunotherapy (Hagerstown, Md. : 1997)

VOLUME: 29

Page Numbers: 143-50

Journal Abbreviation: J. Immunother.

ISSN: 1524-9557

DAY: 18

MONTH: 03

YEAR: 2008

Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9706083

Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Keywords Mesh Terms:

KEYWORDS: Toll-Like Receptor 9

MESH TERMS: immunology

Chemical & Substance for Abstract: Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent. Information

Substance Name: Picibanil

Registry Number: 39325-01-4

Grant and Affiliation Information for Antitumor effect of OK-432-derived DNA: one of the active constituents of OK-432, a streptococcal immunotherapeutic agent.

AFFILIATION: Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, Tokushima, Japan.

Country: United States

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MEDLINETA: J Immunother

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