High level of MUC1 in serum of ovarian and breast cancer patients inhibits huHMFG-1 dependent cell-mediated cytotoxicity (ADCC)

María Moreno, Hetty J. Bontkes, Rik J. Scheper, Peter Kenemans, René H.M. Verheijen, Silvia von Mensdorff-Pouilly

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Abstract

The huHMFG-1 (AS1402) antibody is a humanised IgG1 directed against MUC1 and is currently in clinical trials for the treatment of breast carcinoma. Adenocarcinomas over-express and shed MUC1, and high MUC1 serum levels are associated with progressive disease. Here, we have investigated the effects of MUC1 present in sera from breast and ovarian cancer patients and that of NK cells on in vitro huHMFG-1-mediated ADCC, performed with and without the addition of various cytokines. Screening for patients with high levels of NK cells bearing the FcγRIIIa-158V polymorphism, adjusting the dosage to circulating levels of MUC1 and co-administration of NK cell activating cytokines may increase the efficacy of huHMFG-1 treatment.

Original languageEnglish
Pages (from-to)47-55
Number of pages9
JournalCancer Letters
Volume257
Issue number1
DOIs
Publication statusPublished - 8 Nov 2007

Keywords

  • ADCC
  • MUC1
  • NK cells
  • huHMFG-1 monoclonal antibody

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