Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity

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Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity
T W Kim; Tae Young Lee; H C Bae; J H Hahm; Yang Hyun Kim; C Park; T H Kang; C J Kim; M H Sung; Haryoung Poo
Bibliographic Citation
Journal of Immunology, vol. 179, no. 2, pp. 775-780
Publication Year
We analyzed the in vivo tumor regression activity of high molecular mass poly-gamma-glutamate (gamma-PGA) from Bacillus subtilis sups. chungkookjang. C57BL/6 mice were orally administered 10-, 100-, or 2000-kDa gamma-PGA or beta-glucan (positive control), and antitumor immunity was examined. Our results revealed higher levels of NK cell-mediated cytotoxicity and IFN-gamma secretion in mice treated with higher molecular mass gamma-PGA (2000 kDa) vs those treated with lower molecular mass gamma-PGA (10 or 100 kDa) or beta-glucan. We then examined the effect of oral administration of 10- or 2000-kDa gamma-PGA on protection against B16 tumor challenge in C57BL/6 mice. Mice receiving high molecular mass gamma-PGA (2000 kDa) showed significantly smaller tumor sizes following challenge with the MHC class I-down-regulated tumor cell lines, B16 and TC-1 P3 (A15), but not with TC-1 cells, which have normal MHC class I expression. Lastly, we found that gamma-PGA-induced antitumor effect was decreased by in vivo depletion of NK cells using mAb PK136 or anti-asialo GM1 Ab, and that was completely blocked in NK cell-deficient B6 beige mice or IFN-gamma knockout mice. Taken together, we demonstrated that oral administration of high molecular mass gamma-PGA (2000 kDa) generated significant NK cell-mediated antitumor activity in mice bearing MHC class I-deficient tumors.
oral drug administrationadministration, oral
Amer Assoc Immunologists
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Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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