Antibody-based fusion proteins to target death receptors in cancer

Marco de Bruyn, Edwin Bremer*, Wijnand Helfrich

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

51 Citations (Scopus)

Abstract

Ideally, an immunotoxin should be inactive 'en route', acquire activity only after tumor cell surface binding and have no off-target effects towards normal cells. In this respect, antibody-based fusion proteins that exploit the tumor-selective pro-apoptotic death ligands sFasL and sTRAIL appear promising. Soluble FasL largely lacks receptor-activating potential, whereas sTRAIL is inactive towards normal cells. Fusion proteins in which an anti-tumor antibody fragment (scFv) is fused to sFasL or sTRAIL prove to be essentially inactive when soluble, while gaining potent anti-tumor activity after selective binding to a predefined tumor-associated cell surface antigen. Importantly, off-target binding by scFv:sTRAIL to normal cells showed no signs of toxicity. In this review, we highlight the rationale and perspectives of scFv:TRAIL/scFv:sFasL based fusion proteins for cancer therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalCancer letters
Volume332
Issue number2
DOIs
Publication statusPublished - 28-May-2013

Keywords

  • TRAIL
  • FasL
  • scFv
  • Immune therapy
  • Targeting
  • Apoptosis
  • TUMOR-NECROSIS-FACTOR
  • FAS-INDUCED APOPTOSIS
  • CHRONIC LYMPHOCYTIC-LEUKEMIA
  • TRAIL-INDUCED APOPTOSIS
  • MEDIATED APOPTOSIS
  • MONOCLONAL-ANTIBODY
  • IN-VIVO
  • RESTRICTED ACTIVATION
  • PROAPOPTOTIC ACTIVITY
  • CASPASE ACTIVATION

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