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Toll‐Like Receptor‐Targeting Immunotherapy for Oral Cancer
Author(s) -
Okamoto Masato,
Sato Mitsunobu
Publication year - 2004
Publication title -
oral science international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.256
H-Index - 13
eISSN - 1881-4204
pISSN - 1348-8643
DOI - 10.1016/s1348-8643(04)80001-6
Subject(s) - lipoteichoic acid , cancer immunotherapy , cancer , immunotherapy , tlr4 , toll like receptor , cancer cell , receptor , monoclonal antibody , immunology , cancer vaccine , cancer research , antibody , innate immune system , biology , chemistry , immune system , biochemistry , bacteria , genetics , staphylococcus aureus
It is important to augment the anti‐cancer host response in cancer treatment. Recent studies have suggested that the signaling that occurs via the Toll‐like receptors(TLRs), which are newly identified receptor molecules recognizing many pathogens, are involved in the induction of anti‐cancer immunity. OK‐432, a penicillin‐killed and lyophilized preparation of Streptococcus pyogenes , is being successfully used as an immunotherapeutic agent in many types of malignancies. However, the molecular mechanisms of OK‐432, a whole bacterial preparation, and the active components which make it effective against cancer, remain uncertain. We have succeeded in isolating the active component of OK‐432 (lipoteichoic acid‐related molecule, OK‐PSA) by affinity chromatography of a butanol extract of OK‐432 on the CNBr‐activated sepharose 4B bound TS‐2 monoclonal antibody that neutralizes the interferon(IFN)‐ γ ‐inducing activity of OK‐432. OKPSA induced Th1‐type cytokines both in human and in mice, and elicited an anti‐cancer effect in tumorbearing mice via TLR4. Furthermore, our clinical study revealed that TLR4 signaling is intimately involved in the anti‐cancer effect achieved by OK‐432 in patients with oral cancer. We elucidated that OK‐432 is first captured and digested by phagocytes, such as dendritic cells and macrophages, and then its active component, OK‐PSA, which is released from the phagocytes, stimulates TLR4 signaling. It is strongly suggested that OK‐PSA is the molecule most responsible for the anti‐cancer effect of OK‐432, and that TLR4 may be a definite molecular target for cancer immunotherapy with OK‐432/OK‐PSA.