Journal
GLYCOBIOLOGY
Volume 21, Issue 8, Pages 1097-1107Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwr048
Keywords
anti-carbohydrate; biomarker; in vivo therapy; monoclonal antibody; Tn antigen
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Funding
- Mrs. Berta Kamprad Foundation
- Gunnar Nilsson Cancer Foundation
- IngaBritt and Arne Lundberg Foundation
- Franke and Margareta Bergquist Foundation
- Swedish Cancer Society
- Swedish Research Council within Nation Health Service
- Lund University Hospital Foundations
- Royal Physiographical Society in Lund
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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.
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