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

Abstract

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.

• Authors: Tae Woo Kim, Tae Young Lee, Hyun Cheol Bae, Jeong Ho Hahm, Yang Hyun Kim, Chung Park, Tae Heung Kang, Chul Joong Kim, Moon Hee Sung, Haryoung Poo
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 179 Issue 2 Pg. 775-80 (Jul 15 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17617566 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glutamates
• Histocompatibility Antigens Class I
• Interferon-gamma

Topics

• Administration, Oral
• Animals
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Glutamates (administration & dosage)
• Histocompatibility Antigens Class I (immunology)
• Immunity, Cellular (drug effects)
• Interferon-gamma (drug effects)
• Killer Cells, Natural (drug effects)
• Lymphocyte Activation (drug effects)
• Mice
• Mice, Inbred C57BL
• Neoplasms, Experimental (drug therapy, immunology)