Oral administration of high molecular mass poly-gamma-glutamate induces NK cell-mediated antitumor immunity.
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.
Kim
Tae Woo
TW
Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Gyeonggi-Do, Korea.
Lee
Tae Young
TY
Bae
Hyun Cheol
HC
Hahm
Jeong Ho
JH
Kim
Yang Hyun
YH
Park
Chung
C
Kang
Tae Heung
TH
Kim
Chul Joong
CJ
Sung
Moon Hee
MH
Poo
Haryoung
H
D000284:Administration, Oral; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005971:Glutamates / Q000008:administration & dosage*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology
D005971:Glutamates; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma