title: Antitumor activity of orally administered maitake α-glucan by stimulating antitumor immune response in murine tumor.
abstract: Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma. Orally administered YM-2A enhanced antitumor immune response by increasing INF-γ-expressing CD4+ and CD8+ cells in the spleen and INF-γ-expressing CD8+ cells in tumor-draining lymph nodes. In vitro study showed that YM-2A directly activated splenic CD11b+ myeloid cells, peritoneal macrophages and bone marrow-derived dendritic cells, but did not affect splenic CD11b- lymphocytes or colon-26 tumor cells. YM-2A is more slowly digested by pancreatic α-amylase than are amylopectin and rabbit liver glycogen, and orally administered YM-2A enhanced the expression of MHC class II and CD86 on dendritic cells and the expression of MHC class II on macrophages in Peyer's patches. Furthermore, in vitro stimulation of YM-2A increased the expression of pro-inflammatory cytokines in Peyer's patch CD11c+ cells. These results suggest that orally administered YM-2A can activate dendritic cells and macrophages in Peyer's patches, inducing systemic antitumor T-cell response. Thus, YM-2A might be a candidate for an oral therapeutic agent in cancer immunotherapy.
authors.affiliation: Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Masuda
authors.affiliation: Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakayama
authors.affiliation: Research and Development Department, Yukiguni Maitake Co., Ltd., Niigata, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Research and Development Department, Yukiguni Maitake Co., Ltd., Niigata, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Naito
authors.affiliation: Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
authors.forename: Morichika
authors.initials: M
authors.lastname: Konishi
mesh_terms: D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005936:Glucans / Q000008:administration & dosage / Q000494:pharmacology*; D048691:Grifola / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D055292:Pancreatic alpha-Amylases / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D016207:Cytokines; D005936:Glucans; D055292:Pancreatic alpha-Amylases