Related Experiment Video

Updated: May 28, 2026

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
08:46

A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells

Published on: November 12, 2019

CD47-signal regulatory protein-α (SIRPα) interactions form a barrier for antibody-mediated tumor cell destruction

Xi Wen Zhao1, Ellen M van Beek, Karin Schornagel

  • 1Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.

Proceedings of the National Academy of Sciences of the United States of America
|November 2, 2011
PubMed

Insights

Cancer therapies using monoclonal antibodies can be enhanced by blocking the CD47-SIRPα interaction. This interaction normally prevents immune cells from destroying cancer cells, but inhibiting it boosts antibody effectiveness against tumors.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Therapeutics

Background:

  • Monoclonal antibodies are key cancer treatments, targeting tumor cells for immune destruction.
  • The CD47-SIRPα axis on tumor and myeloid cells inhibits antibody-mediated cancer cell killing.

Purpose of the Study:

  • To investigate the role of CD47-SIRPα interactions in limiting antibody-mediated tumor cell elimination.
  • To explore targeting CD47-SIRPα as a strategy to enhance cancer immunotherapy.

Main Methods:

  • Utilized mouse models lacking SIRPα cytoplasmic tail for in vivo studies.
  • Performed in vitro assays with CD47 knockdown and antagonistic antibodies against CD47/SIRPα.
  • Analyzed trastuzumab therapy response in breast cancer patients concerning CD47 expression.

Main Results:

  • Mice lacking SIRPα cytoplasmic tail showed enhanced antibody-mediated melanoma cell clearance.
  • Blocking CD47-SIRPα interactions significantly increased phagocyte-mediated killing of trastuzumab-treated breast cancer cells.
  • Breast cancer patient response to trastuzumab correlated with tumor cell CD47 expression.

Conclusions:

  • CD47-SIRPα interactions represent a homeostatic mechanism restricting antibody-driven tumor cell killing.
  • Targeting CD47-SIRPα interactions, potentially with antagonistic antibodies, can potentiate the efficacy of therapeutic antibodies in cancer treatment.

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