Use of Bifunctional Immunotherapeutic Agents to Target Breast Cancer

Abstract

An anti-cancer strategy has been developed that relies on a synthetic ligand to 1)specitically target the cell surface, 2)recruit antibodies to the tumor cell, and 3) subsequently initiate a cytotoxic immune response. This small-molecule is composed of two distinct motifs: an RGD peptomimetric that binds with high affinity to the alpha (v) beta(3) integrin (a cell-surface marker found to be upregulated in numerous cancers) and the alpha-Gal trisaccharide antigen that interacts with endogenous human antibody. Using out bifunctional conjugate, we found that the multivalent properties of anti-Gal binding can be exploited to triger complement-mediated lysis of only those cells that display elevated levels of alpha (v) beta (3) integrin. The ability of anti-Gal to cause complement-medicated lysis depends on the concentration of alpha-Gal epitopes displayed on the cell surface.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2007
Accession Number
ADA518343

Entities

People

  • April Weir
  • Coby B. Carlson
  • Emily C Dykhuizen

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Antibodies
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Medical Personnel
  • Molecules
  • Neoplasms
  • Organic Chemistry
  • Small Molecules
  • Targeting
  • Targets
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Immunology
  • Molecular and Cellular Biochemistry
  • Oncology (Cancer Research).