Soluble branched (1,4)-beta-D-glucans from Acetobacter species enhance antitumor activities against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response.

We previously found that an extracellular polysaccharide, AC-1, produced by Acetobacter polysaccharogenes composed of (1,4)-beta-D-glucan with branches of glucosyl residues showed a strong activity to induce production of interleukin (IL)-12 p40 and tumor necrosis factor-alpha by macrophage cell lines in vitro via Toll-like receptor-4 signaling. In the present study, we examined the effects of oral administration of AC-1 on protection against 2 types of murine B16 melanoma lines, major histocompatibility complex (MHC) class I-negative B16L and MHC class I gene-transfected B16K(b) cells. Mice were inoculated subcutaneously with B16L or B16K(b) cells on day 0 and administrated intragastrically with AC-1 or PBS once every 5 days from 1 day before tumor inoculation. The tumor growth was severely retarded in AC-1-treated mice after subcutaneous inoculation with B16L or B16K(b) cells. The AC-1-treated mice showed augmented natural killer (NK) cell activity against B16L cells, and in vivo depletion of NK cells by antiasialoGM1 antibody (Ab) treatment abrogated the antitumor activity in AC-1-treated mice. On the other hand, AC-1-treated mice inoculated with B16K(b) cells developed a significantly higher level of cytotoxic T-lymphocyte response against B16K(b) cells, and in vivo depletion of CD8(+) T cells by anti-CD8 mAb treatment abrogated the antitumor activity. Thus, AC-1 augmented antitumor activity against different tumors via augmentation of different antitumor mechanisms. These results suggest a possible prophylactic application of AC-1 for human neoplasms irrespective of expression levels of their MHC class I molecules. (c) 2005 Wiley-Liss, Inc.