[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].
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.
Oshikawa
Tetsuya
T
Second Dept. of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry.
Okamoto
Masato
M
Ahmed
Sharif Uddin
SU
Tano
Tomoyuki
T
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000276:Adjuvants, Immunologic; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D066298:In Vitro Techniques; D015552:Injections, Intralesional; D007376:Interleukin-2 / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D010844:Picibanil / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000502:physiology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D010844:Picibanil