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T cells taken from patients and engineered to recognise the MAGE-A4 protein shrank tumours in about four in ten patients with advanced synovial sarcoma, leading to the first approval of a TCR T-cell therapy for any solid cancer.
Single-arm phase 2 trial of 52 patients (44 with synovial sarcoma, 8 with myxoid/round cell liposarcoma) who were HLA-A*02 positive with MAGE-A4-expressing tumours, previously treated with anthracycline or ifosfamide, treated with a single infusion of afamitresgene autoleucel (afami-cel), autologous T cells expressing an affinity-enhanced MAGE-A4-specific T-cell receptor, after lymphodepleting chemotherapy. Primary endpoint was objective response rate.
The response rate was 37% overall and 39% in synovial sarcoma, with a median duration of response of about 12 months. Cytokine release syndrome occurred in about 70% but was mostly low grade. It led to FDA accelerated approval in 2024 (Tecelra), the first TCR-T and the first engineered cell therapy approved for a solid tumour.
Patients with advanced synovial sarcoma, a rare cancer of young adults with few effective drugs, now have an approved cell therapy that produces responses lasting about a year in a substantial minority, if their tissue type and tumour antigen match. It proves that engineered T cells can work against a solid tumour when a good target is present, which had been elusive. It is not a cure for most, requires specialised centres, and only a minority of patients are eligible.
Shares Adaptimmune, Letetresgene autoleucel, TCR-T cell therapy, Sarcomas (soft tissue, bone, GIST).
Shares Letetresgene autoleucel, MAGE-A4, Afamitresgene autoleucel, Synovial sarcoma.
Shares Afamitresgene autoleucel, Synovial sarcoma, TCR-T cell therapy, Sarcomas (soft tissue, bone, GIST).
Shares Letetresgene autoleucel, Afamitresgene autoleucel, Rare and paediatric cancers without markets, Sarcomas (soft tissue, bone, GIST).
Shares MAGE-A4, Afamitresgene autoleucel, Synovial sarcoma.
Shares MAGE-A4, Afamitresgene autoleucel, TCR-T cell therapy, Manufacturing cost and time for living and radioactive medicines.
Shares MAGE-A4, TCR-T cell therapy.