CD47 and SIRP-alpha blockade
Drugs that remove the 'don't eat me' signal cancer cells show to macrophages, so the immune system's scavenger cells can engulf them; the lead programme was halted for safety.
Overview
CD47 on tumour cells binds SIRP-alpha on macrophages and stops them engulfing the cell. Antibodies and fusion proteins that block the axis (magrolimab, evorpacept and others) boost antibody-dependent phagocytosis, especially with rituximab or azacitidine. Magrolimab's phase 3 programme in myelodysplastic syndromes and acute myeloid leukaemia was stopped in 2024 after excess deaths, but SIRP-alpha-directed agents and bispecifics continue in lymphoma and solid tumours.
How it works
Blocking CD47 or SIRP-alpha removes the inhibitory signal so macrophages phagocytose opsonised tumour cells; agents are engineered to spare red cells, which also express CD47.
- Engages macrophages, a different arm from T-cell checkpoints
- Synergy with therapeutic antibodies
- Anaemia from red cell CD47
- Magrolimab programme stopped for safety
- No approval yet
Latest papers
topQuery for this technology: (TITLE:"CD47 and SIRP-alpha blockade" OR ABSTRACT:"CD47 and SIRP-alpha blockade") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about CD47 and SIRP-alpha blockade, not a curated reading list.
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