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Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis

Eunee Koh1, Eun Jung Lee2, Gi-Hoon Nam1

  • 1Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea.

Biomaterials
|January 14, 2017
PubMed

Insights

Engineered exosomes carrying signal regulatory protein α (SIRPα) variants block the CD47 "don't eat me" signal on tumors. This enhances macrophage tumor cell engulfment and primes an effective anti-tumor T cell response for cancer therapy.

Area of Science:

  • Immunology
  • Oncology
  • Biotechnology

Background:

  • CD47, a "don't eat me" signal, is overexpressed on tumor cells, inhibiting macrophage phagocytosis via interaction with SIRPα.
  • This CD47-SIRPα interaction forms a significant barrier to innate immune clearance of cancer cells.

Purpose of the Study:

  • To develop an exosome-based immune checkpoint blockade targeting the CD47-SIRPα interaction.
  • To evaluate the efficacy of SIRPα-exosomes in enhancing anti-tumor immunity.

Main Methods:

  • Engineered exosomes harboring signal regulatory protein α (SIRPα) variants (SIRPα-exosomes) were developed.
  • The ability of SIRPα-exosomes to induce tumor phagocytosis and anti-tumor T cell responses was assessed in vitro and in vivo.
  • Tumor growth inhibition and T cell infiltration were evaluated in syngeneic mouse models.

Main Results:

  • SIRPα-exosomes effectively disrupted the CD47-SIRPα interaction, leading to increased macrophage-mediated tumor cell engulfment.
  • Therapy with SIRPα-exosomes resulted in significant inhibition of tumor growth in vivo.
  • SIRPα-exosome treatment promoted substantial T cell infiltration into tumors, indicating activation of adaptive immunity.

Conclusions:

  • Exosome-based delivery of SIRPα variants offers a promising strategy for immune checkpoint blockade against CD47.
  • This approach unleashes both innate (phagocytosis) and adaptive (T cell response) anti-tumor immunity.
  • Exosome-based platforms have broad potential for enhancing the therapeutic efficacy of membrane-associated protein therapeutics.
Keywords:
CD47Cancer immunotherapyExosomePhagocytosisSignal regulatory protein α

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