Enhancement of reactivity of anti-MUC1 core protein antibody and killing activity of anti-MUC1 cytotoxic T cells by deglycosylation of target tissues or cells.
MUC1 mucin core protein contains an important tumor-associated peptide antigen that can induce cytotoxic T cells (CTLs) in vivo, although this antigen is generally masked by mucin-type glycans. To reveal the precise expression pattern of MUC1 protein in normal and neoplastic gastric tissues, we performed immunohistochemical staining of periodic acid-treated tissue sections with an anti-MUC1 core protein monoclonal antibody (mAb), MUSE11. In non-cancerous tissues, the deep portion of fundic glands and the luminal surface were predominantly immunostained in normal and metaplastic glands, respectively. In cancerous tissues, the incidence of positivity for MUC1 protein varied from 67% to 88%, depending on histological type. This frequent expression of MUC1 protein in cancer tissues after periodic acid treatment suggested that deglycosylation may be of use for exposing the target antigen of anti-MUC1 CTLs. Accordingly, we then examined the effect of benzyl-alpha-GalNAc, an inhibitor of O-glycan biosynthesis, on the expression of MUC1 protein and sensitivity to an anti-MUC1 CTL line, designated TS, in gastric cancer JRST cells. After incubation with benzyl-alpha-GalNAc, the reactivity of mAb MUSE11 with JRST cells and their sensitivity of TS were clearly increased. These findings suggest that deglycosylation may offer an important strategy for enhancing anti-tumor immunity in patients with gastric cancer.
Hinoda
Y
Y
First Department of Internal Medicine, Sapporo Medical University, Japan.
Takahashi
T
T
Hayashi
T
T
Suwa
T
T
Makiguchi
Y
Y
Itoh
F
F
Adachi
M
M
Imai
K
K
D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000937:Antigen-Antibody Reactions; D001593:Benzyl Compounds / Q000494:pharmacology; D002460:Cell Line; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018396:Mucin-1 / Q000235:genetics / Q000276:immunology*; D009077:Mucins / Q000378:metabolism; D009363:Neoplasm Proteins / Q000276:immunology*; D011134:Polysaccharides / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D001593:Benzyl Compounds; D018396:Mucin-1; D009077:Mucins; D009363:Neoplasm Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; C080739:benzyl-alpha-N-acetylgalactosamine; D000116:Acetylgalactosamine