A new murine IgG1 anti-Tn monoclonal antibody with in vivo anti-tumor activity

被引:38
作者
Welinder, Charlotte [2 ]
Baldetorp, Bo [2 ]
Borrebaeck, Carl [3 ]
Fredlund, Britt-Marie [1 ]
Jansson, Bo [1 ]
机构
[1] BioInvent Int AB, SE-22370 Lund, Sweden
[2] Lund Univ, Dept Oncol, Lund, Sweden
[3] Lund Univ, Dept Immunotechnol, Lund, Sweden
基金
瑞典研究理事会;
关键词
anti-carbohydrate; biomarker; in vivo therapy; monoclonal antibody; Tn antigen; HELIX-POMATIA LECTIN; HUMAN BREAST-CANCER; LYMPH-NODE METASTASES; COLON-CANCER; HPA BINDING; CELL-LINES; CARBOHYDRATE ANTIGENS; PREDICTIVE-VALUE; HUMAN TISSUES; BLOOD-GROUP;
D O I
10.1093/glycob/cwr048
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Tn antigen (GalNAc alpha-O-Ser/Thr) is heterogeneously synthesized by a variety of tumors and contains an epitope defined by lectins and antibodies as a cluster of alpha GalNAc carbohydrates synthesized within a peptide sequence, which is rich in serine and/or threonine. The Tn antigen has been utilized as a target in vaccine experiments and also used as a biomarker for prognosis of different cancer forms. In this paper, we present a new monoclonal antibody, GOD3-2C4, with the clear hallmarks of an anti-Tn antibody. It was generated through somatic cell hybridization after immunization of a mouse with a tumor cell line and a Tn carrying mucin. The antibody recognizes synthetic Tn antigen and binds breast, colon, lung, ovarian and pancreas cancer. The GOD3-2C4 antibody has antibody-dependent cellular cytotoxicity activity against Jurkat cells in vitro, and for the first time, it can be shown that an anti-Tn antibody has a significant in vivo effect on a human cancer cell line grown as a xenograft in severe combined immunodeficiency mice.
引用
收藏
页码:1097 / 1107
页数:11
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