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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.
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.
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.
Evorpacept is an experimental immune checkpoint modulator from ALX Oncology in phase 3 trials for gastric & gastro-oesophageal junction cancer, HR-positive / HER2-negative breast cancer and HER2-positive breast cancer, with its target not yet stated publicly.
The first 'don't eat me' signal blocker. Gilead paid $4.9B for it; it was stopped in 2024 after trials showed more deaths, not fewer.
Query 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.
Shares A Study of Evorpacept (ALX148) in Patients With Advanced HER2+ Gastric Cancer (ASPEN-06), Evorpacept (ALX148) in Combination With Pembrolizumab in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-03), Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04), Evorpacept.
Shares Magrolimab, CD47, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Magrolimab, CD47, Acute myeloid leukaemia, Diffuse large B-cell lymphoma.
Shares Magrolimab, Higher-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS).
Shares Higher-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Higher-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Secondary and therapy-related acute myeloid leukaemia, Higher-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.
Shares Higher-risk myelodysplastic syndromes, Myelodysplastic syndromes / neoplasms (MDS), Acute myeloid leukaemia.