Open AccessAnti‐tumor effect of the anti‐KL‐6/MUC1 monoclonal antibody through exposure of surface molecules by MUC1 capping
Author(s) -
Doi Mihoko,
Yokoyama Akihito,
Kondo Keiichi,
Ohnishi Hiroshi,
Ishikawa Nobuhisa,
Hattori Noboru,
Kohno Nobuoki
Publication year - 2006
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00183.x
Subject(s) - muc1 , monoclonal antibody , cytotoxic t cell , antigen , cell adhesion molecule , immunotherapy , cancer cell , cell culture , cancer research , antibody , cancer immunotherapy , biology , epithelial cell adhesion molecule , cell , cluster of differentiation , cell adhesion , chemistry , microbiology and biotechnology , cancer , immunology , biochemistry , in vitro , immune system , genetics
Human polymorphic epithelial mucin (MUC1) is a heavily glycosylated large protein that is frequently overexpressed on the surface of many human adenocarcinomas. Studies using monoclonal antibodies (mAb) identified MUC1 as a tumor‐associated antigen that has been intensely studied as a target for cancer immunotherapy. We previously identified a mouse IgG 1 mAb that recognizes a sialylated sugar chain, designated as KL‐6, classified in ‘Cluster 9 (MUC1)’. Using the anti‐KL‐6 mAb, we investigated antitumor effects of anti‐MUC1 mAb on breast cancer cell lines expressing MUC1 abundantly. We showed that anti‐KL‐6 mAb induced capping of MUC1 and facilitated E‐cadherin‐mediated cell–cell interaction in the breast cancer cell lines YMB‐S and ZR‐75‐1S, which proliferate in suspension culture without aggregation. Moreover, anti‐KL‐6 mAb enhanced the cytotoxic activity of lymphokine‐activated killer cells. These results indicate that the capping of MUC1 restores cell surface proteins, such as adhesion molecules and tumor antigens, to work in cell–cell interactions, leading to inhibition of tumor proliferation due to cell–cell adhesion and increased accessibility to effector cells that are needed to kill tumor cells. ( Cancer Sci 2006)