Related Experiment Video

Updated: Jun 20, 2025

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

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Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

Chenyang Jiang1,2, Hao Sun3, Zhongxing Jiang1

  • 1Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Frontiers in Oncology
|July 23, 2024
PubMed

Insights

Recent clinical trial setbacks for CD47-SIRPα-targeted therapies, including Magrolimab and Evorpacept in myelodysplastic syndromes, raise concerns about their development feasibility. This review examines challenges and proposes solutions for advancing CD47-SIRPα drug development.

Area of Science:

  • Immunology
  • Oncology
  • Drug Development

Background:

  • CD47, an innate immune checkpoint, emerged as a promising therapeutic target, likened to PD-1.
  • Early clinical development and industry investments fueled optimism for CD47-targeted therapies.

Purpose of the Study:

  • To review the challenges in developing CD47-SIRPα-targeted drugs.
  • To analyze factors contributing to recent clinical trial setbacks.
  • To discuss future perspectives and solutions for CD47-SIRPα drug development.

Main Methods:

  • Literature review of CD47-SIRPα drug development.
  • Analysis of recent clinical trial outcomes (Magrolimab, Evorpacept).
  • Discussion of industry trends and investment landscape.

Main Results:

  • Recent Phase 3 (ENHANCE) and Phase 2 (ASPEN-02) trials for CD47-targeted therapies in myelodysplastic syndromes (MDS) reported failures.
  • These setbacks have introduced significant doubt regarding the clinical utility of targeting CD47 in oncology.
  • The efficacy of CD47-SIRPα blockade as a monotherapy or in combination requires further investigation.

Conclusions:

  • Developing CD47-SIRPα-targeted drugs faces significant hurdles.
  • Understanding the complex tumor microenvironment and immune evasion mechanisms is crucial.
  • Future strategies may involve combination therapies, novel target identification, or refined patient selection to overcome current challenges.
Keywords:
SIRPαcancer immunotherapycd47monoclonal antibodysignaling pathwaytargeted therapy

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