Inhibition of cancer cell growth by anti-Tn monoclonal antibody MLS128.
Tn-antigens are generally masked by covalently linked carbohydrates but are exposed in most primary and metastatic epithelial malignant tumors, providing sensitive markers for detection of carcinoma. Here, therapeutic potentials of tumor-associated carbohydrate antigen-specific antibodies were investigated. MLS128, an anti-Tn monoclonal antibody, binds to a carbohydrate epitope consisting of three consecutive Tn-antigens (GalNAcalpha-Ser/Thr). MLS128 treatment significantly inhibited colon and breast cancer cell growth. MLS128 bound to 110-210 kDa glycoproteins on the cell surface. MLS128 treatment caused down-regulation of insulin-like growth factor-I receptor and epidermal growth factor receptor in LS180 colon cancer cells, suggesting that MLS128-inhibited cancer cell growth is in part mediated by down-regulation of growth factor receptors. This study provides the first insights into the potential use of this particular type of anti-Tn antigen antibodies as a cancer therapeutic.
Morita
Noriyuki
N
Department of Applied Biochemistry, Tokai University School of Engineering, Hiratsuka, Kanagawa, Japan.
Yajima
Yukiko
Y
Asanuma
Hideki
H
Nakada
Hiroshi
H
Fujita-Yamaguchi
Yoko
Y
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; C040286:Tn antigen