Anti-idiotypic antibody mimicking a T-antigen-specific lectin inhibits human epithelial tumor cell proliferation

Immunol Cell Biol. 2010 Nov-Dec;88(8):787-94. doi: 10.1038/icb.2010.49. Epub 2010 Apr 20.

Abstract

Cancer-associated mucins show frequent alterations of oligosaccharide chain profile. Terminal structures may be deleted, thereby exposing normally 'cryptic' structures such as Tn (GalNAcα-O-Ser/Thr) and T antigen (Galβ1-3GalNAcα-O-Ser/Thr). Overexpression of these commonly hidden glycoforms, and reduced level of naturally occurring anti-T or anti-Tn antibodies, is associated with epithelial tumor progression and aggressiveness. The lectin from the common edible mushroom Agaricus bisporus (ABL) shows high affinity binding to T antigen, and reversible noncytotoxic inhibitory effect on epithelial tumor cell proliferation. The aim of this study was to induce immune response with tumor-associated glycan specificity and biological activity similar to those of ABL. An anti-idiotypic (Id) antibody strategy was developed using ABL as first template. ABL was purified by affinity chromatography and assayed as immunogen in rabbit. Rabbit IgG was purified from anti-ABL serum using a protein G column, and specific anti-ABL IgG was obtained by affinity chromatography using immobilized ABL. Affinity-purified anti-ABL IgG contained an antibody fraction that recognizes the carbohydrate-binding site of ABL. This IgG was used as immunogen in mouse to yield anti-Id antibody recognizing tumor-associated glycans such as Tn and T antigen. Competitive assays showed that α-anomeric GalNAc is the main binding subsite of anti-Id antibody in glycan recognition. Anti-Id antibody bound human epithelial tumor cells, as shown by cell enzyme-linked immunosorbent assay and immunofluorescence. Anti-Id antibody raised by immunization with affinity-purified anti-ABL IgG had antiproliferative effect on human epithelial tumor cells through apoptosis induction similar to that of ABL. The anti-Id immune response developed here has potential application in cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricus / immunology
  • Animals
  • Antibodies, Anti-Idiotypic / pharmacology*
  • Antigens, Viral, Tumor / metabolism
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Carcinoma / drug therapy
  • Carcinoma / immunology*
  • Carcinoma / pathology
  • Cell Growth Processes / drug effects
  • Cell Growth Processes / immunology
  • Cells, Cultured
  • Chromatography, Affinity
  • Epitopes / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Immunization
  • Immunoglobulin G / immunology
  • Lectins / immunology*
  • Lectins / isolation & purification
  • Lectins / metabolism
  • Mice
  • Protein Binding / immunology
  • Rabbits

Substances

  • Agaricus lectins
  • Antibodies, Anti-Idiotypic
  • Antigens, Viral, Tumor
  • Epitopes
  • Immunoglobulin G
  • Lectins