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 th is antigen is generally masked by mucin-type glycans, To reveal the pr ecise expression pattern of MUC1 protein in normal and neoplastic gast ric tissues. we performed immuno-histochemical staining of periodic ac id-treated tissue sections with an anti-MUC1 core protein monoclonal a ntibody (mAb), MUSE11. In non-cancerous tissues, the deep portion of f undic 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%, d epending on histological type. This frequent expression of MUC1 protei n in cancer tissues after periodic acid treatment suggested that degly cosylation 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 prot ein and sensitivity to an anti-MUC1 CTL line, designated TS, in gastri c cancer JRST cells. After incubation with benzyl-alpha-GalNAc. the re activity of mAb MUSE11 with JRST cells and their sensitivity of TS wer e clearly increased, These findings suggest that deglycosylation may o ffer an important strategy for enhancing anti-tumor immunity in patien ts with gastric cancer.