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Blockade of CD47 or SIRPα: a new cancer immunotherapy

Yoji Murata1, Yasuyuki Saito1, Takenori Kotani1

  • 1Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine , Japan.

Expert Opinion on Therapeutic Targets
|August 18, 2020
PubMed

Insights

Targeting the CD47-Signal regulatory protein α (SIRPα) axis can enhance cancer immunotherapy by blocking tumor cells from evading immune cells. This review explores current strategies and future directions for CD47-SIRPα-targeted cancer treatments.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • The CD47-Signal regulatory protein α (SIRPα) signaling pathway is a critical checkpoint that inhibits phagocytosis by macrophages, a key component of the innate immune system.
  • Tumor cells often overexpress CD47, which binds to SIRPα on macrophages, thereby preventing their elimination and promoting immune evasion.
  • Understanding this interaction is crucial for developing novel cancer immunotherapies.

Discussion:

  • The CD47-SIRPα axis represents a significant target for cancer therapy, aiming to unleash the phagocytic potential of macrophages against tumors.
  • Antibodies and other therapeutic modalities targeting this interaction are being investigated for their clinical efficacy.
  • Current strategies face challenges, including potential on-target, off-tumor toxicities and the need for optimized delivery and dosing.

Key Insights:

  • Blocking the CD47-SIRPα interaction can restore macrophage-mediated phagocytosis of cancer cells.
  • Therapeutic antibodies targeting CD47 have shown promise in preclinical models, demonstrating anti-tumor activity.
  • Combination therapies involving CD47 blockade alongside other immunotherapies may offer synergistic benefits.

Outlook:

  • Further research is needed to refine CD47-SIRPα-targeted therapies, focusing on improving safety profiles and overcoming resistance mechanisms.
  • Exploring alternative therapeutic modalities beyond antibodies, such as small molecule inhibitors or engineered proteins, is a promising avenue.
  • Clinical trials are essential to validate the efficacy and safety of these emerging immunotherapeutic strategies in diverse cancer types.
Keywords:
CD47CancerSIRPαimmunotherapymacrophagephagocytosis

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