NY-ESO-1 c259 T-cell receptor therapy in synovial sarcoma: prolonged persistence and antitumour activity
Engineering patients' own T cells with a receptor recognising the NY-ESO-1 antigen shrank tumours in half of a small group with advanced synovial sarcoma, the first convincing evidence that T-cell receptor therapy can work in a solid tumour.
Overview
Pilot study of 12 patients with HLA-A*02-positive, NY-ESO-1-expressing advanced synovial sarcoma treated with autologous T cells transduced with an affinity-enhanced NY-ESO-1 c259 T-cell receptor after lymphodepleting chemotherapy.
Objective response was 50 percent including one complete response, with responses associated with T-cell persistence and higher lymphodepletion intensity; toxicity included cytokine release syndrome and cytopenias.
- Objective response 6 of 12 patients (50 percent), one complete response.
- Response correlated with T-cell persistence and lymphodepletion dose.
This study opened the path to engineered T-cell receptor therapy in synovial sarcoma, leading to afamitresgene autoleucel targeting MAGE-A4 (SPEARHEAD-1) and its approval in 2024.
- Twelve patients; requires HLA-A*02 and antigen expression.