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

Woo Kim Tae, Young Lee Tae, Cheol Bae Hyun, Ho Hahm Jeong, Hyun Kim Yang, Chung Park, Heung Kang Tae, Joong Kim Chul, Hee Sung Moon, Haryoung Poo

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73 Citations (Scopus)

Abstract

We analyzed the in vivo tumor regression activity of high molecular mass poly-γ-glutamate (γ-PGA) from Bacillus subtilis sups. chungkookjang. C57BL/6 mice were orally administered 10-, 100-, or 2000-kDa γ-PGA or β-glucan (positive control), and antitumor immunity was examined. Our results revealed higher levels of NK cell-mediated cytotoxicity and IFN-γ secretion in mice treated with higher molecular mass γ-PGA (2000 kDa) vs those treated with lower molecular mass γ-PGA (10 or 100 kDa) or β-glucan. We then examined the effect of oral administration of 10- or 2000-kDa γ-PGA on protection against B16 tumor challenge in C57BL/6 mice. Mice receiving high molecular mass γ-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 γ-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-γ knockout mice. Taken together, we demonstrated that oral administration of high molecular mass γ-PGA (2000 kDa) generated significant NK cell-mediated antitumor activity in mice bearing MHC class I-deficient tumors.

Original languageEnglish
Pages (from-to)775-780
Number of pages6
JournalJournal of Immunology
Volume179
Issue number2
DOIs
Publication statusPublished - 2007 Jul 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Tae, W. K., Tae, Y. L., Hyun, C. B., Jeong, H. H., Yang, H. K., Park, C., Tae, H. K., Chul, J. K., Moon, H. S., & Poo, H. (2007). Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity. Journal of Immunology, 179(2), 775-780. https://doi.org/10.4049/jimmunol.179.2.775