Cancer immunotherapy targeting the CD47/SIRPα axis

Area of Science:

• Immunology
• Oncology
• Drug Discovery

Background:

• Cancer immunotherapy success has driven interest in novel targets beyond adaptive immune system stimulation.
• Macrophages and myeloid cells are promising effectors for cancer immunotherapy.
• The CD47/signal regulatory protein alpha (SIRPα) axis acts as a myeloid-specific immune checkpoint, with CD47 highly expressed on cancer cells.

Purpose of the Study:

• To review the role of the CD47/SIRPα axis in cancer immunotherapy.
• To discuss therapeutics targeting the CD47/SIRPα axis currently in development.
• To explore the potential of CD47/SIRPα blockade in various clinical applications.

Main Methods:

• Preclinical models demonstrating CD47/SIRPα axis blockade effects.
• Overview of ongoing preclinical and clinical investigations of CD47/SIRPα targeting therapeutics.
• Analysis of potential synergies with other immunotherapies and clinical indications.

Main Results:

• CD47/SIRPα axis blockade stimulates cancer cell phagocytosis and anti-tumour immune responses in preclinical models.
• Multiple therapeutic strategies targeting this axis are in clinical trials for various malignancies.
• Blocking CD47/SIRPα enhances antigen presentation, linking innate and adaptive immunity.

Conclusions:

• CD47/SIRPα blocking therapies represent a promising strategy for cancer immunotherapy, with potential to synergize with existing treatments.
• The applications of CD47/SIRPα blockade extend beyond cancer to infectious diseases and stem cell transplantation.
• Further clinical investigation is warranted to fully realize the therapeutic potential of targeting this critical immune checkpoint.