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

Glycobiology. 2011 Aug;21(8):1097-107. doi: 10.1093/glycob/cwr048. Epub 2011 Apr 5.

Abstract

The Tn antigen (GalNAc α-O-Ser/Thr) is heterogeneously synthesized by a variety of tumors and contains an epitope defined by lectins and antibodies as a cluster of αGalNAc 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacology*
  • Antigen-Antibody Reactions
  • Antigens, Tumor-Associated, Carbohydrate / immunology*
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / pharmacology
  • Mice
  • Structure-Activity Relationship

Substances

  • Antibodies, Monoclonal
  • Antigens, Tumor-Associated, Carbohydrate
  • Antineoplastic Agents
  • Immunoglobulin G
  • Tn antigen