Related Experiment Video
Updated: Aug 20, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
Targeting the CD47-SIRPα Axis: Present Therapies and the Future for Cutaneous T-cell Lymphoma
1University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Abstract:
The loss of CD47 on aging cells serves as a signal to macrophages to eliminate the target. Therefore, CD47 is a "do-not-eat-me" sign preventing macrophagal phagocytosis via interaction with its ligand SIRPα. Malignant lymphocytes of mycosis fungoides and Sézary syndrome express CD47 highly, thus, being ideal candidates for targeted anti-CD47 therapies. The classes of current anti-CD47-SIRPα therapeutic molecules present in a large variety and include monoclonal antibodies against CD47 and SIRPα, bioengineered SIRPα proteins, miRNAs, and bispecific antibodies. We provided a detailed analysis of all available investigational drugs in a contest of cutaneous T-cell lymphoma. A combination of blockade of the CD47-SIRPα axis and secondary targets in the tumor microenvironment (TME) may improve the clinical efficacy of current immunotherapeutic approaches. We evaluated the possible combination and outlined the most promising one.
Insights
Aging cells lose CD47, signaling macrophages to engulf them. Targeting the CD47-SIRPα axis shows promise for treating mycosis fungoides and Sézary syndrome by blocking this "do-not-eat-me" signal.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- CD47 acts as a "do-not-eat-me" signal, preventing macrophage phagocytosis of cells.
- Aging cells and malignant lymphocytes in mycosis fungoides (MF) and Sézary syndrome (SS) highly express CD47.
- The CD47-SIRPα interaction is a critical pathway in immune evasion.
Purpose of the Study:
- To analyze investigational anti-CD47-SIRPα therapies for cutaneous T-cell lymphoma (CTCL).
- To evaluate potential combination strategies to enhance immunotherapeutic efficacy in CTCL.
- To identify the most promising combination therapy for CTCL.
Main Methods:
- Review of current anti-CD47-SIRPα therapeutic molecules, including antibodies, engineered proteins, and miRNAs.
- Analysis of drug candidates targeting the CD47-SIRPα axis in the context of CTCL.
- Evaluation of combination therapies involving CD47-SIRPα blockade and targeting of other tumor microenvironment factors.
Main Results:
- Various therapeutic molecules targeting the CD47-SIRPα axis are under investigation.
- High CD47 expression on MF and SS cells makes them suitable for anti-CD47 therapies.
- Combination therapy holds potential for improved clinical outcomes in CTCL.
Conclusions:
- Targeting the CD47-SIRPα axis is a promising strategy for CTCL treatment.
- Combining CD47-SIRPα blockade with other immunotherapies may overcome treatment resistance.
- Further research into combination therapies is warranted to optimize clinical efficacy.
More Related Videos
09:08Isolating Human Peripheral Blood Mononuclear Cells and CD4+ T cells from Sézary Syndrome Patients for Transcriptomic Profiling
Published on: October 14, 2021
08:49Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019