Anti-cancer effect of an intratumoral injection of dendritic cells expressing TLR4 in combination with an active component of OK-432 in TLR4-deficient mice
Oshikawa, T.; Okamoto, M.; Ahmed, S.U.; Tano, T.; Yoshida, H.; Sato, M.
Gan to Kagaku Ryoho. Cancer and ChemoTherapy 31(11): 1770-1772
2004
ISSN/ISBN: 0385-0684 PMID: 15553710 Document Number: 570712
A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432. In the in vitro experiments, OK-PSA enhanced expression of MHC class II, CD80 and CD86, as well as IL-12 production on dendritic cells (DCs) were derived from wild-type mice, but not from TLR4-deficient (TLR4-/-) mice. Next we examined the in vivo anti-cancer effect of intratumoral administration of syngeneic DCs followed by OK-PSA against established tumors in mice. Although OK-PSA augmented anti-tumor effect of DC administration in tumor-bearing wild-type mice, anti-tumor effect of DCs and OK-PSA was not significant in TLR4-/- mice. Interestingly, an administration of wild-type mice-derived DCs followed by OK-PSA exhibited a marked anti-tumor effect even in TLR4-/- mice. These findings suggest that OK-PSA may be a potential adjuvant for local DC therapy, and that DC therapy followed by OK-PSA is able to elicit anti-cancer activity even in TLR4-deficient host when TLR4 is expressed only in DCs injected intratumorally.