4.4 Article

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

Journal

GLYCOBIOLOGY
Volume 21, Issue 8, Pages 1097-1107

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/glycob/cwr048

Keywords

anti-carbohydrate; biomarker; in vivo therapy; monoclonal antibody; Tn antigen

Funding

  1. Mrs. Berta Kamprad Foundation
  2. Gunnar Nilsson Cancer Foundation
  3. IngaBritt and Arne Lundberg Foundation
  4. Franke and Margareta Bergquist Foundation
  5. Swedish Cancer Society
  6. Swedish Research Council within Nation Health Service
  7. Lund University Hospital Foundations
  8. 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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