Antitumor Activity Associated with Prolonged Persistence of Adoptively Transferred NY-ESO-1c259T Cells in Synovial Sarcoma

We evaluated safety and activity of autologous T cells expressing NY-ESO-1c259, an affinity-enhanced T cell receptor (TCR) recognizing an HLA-A2-restricted NY-ESO-1/LAGE-1a-derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1c259T cells). Confirmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1c259T cells were present post-infusion in all patients and persisted for at least 6 months in all responders. Most infused NY-ESO-1c259T cells exhibited an effector memory phenotype following the ex vivo expansion, but the persisting pools comprised largely central memory and stem cell memory subsets, which remained polyfunctional and showed no evidence for T cell exhaustion despite persistent tumor burdens. Next generation sequencing of endogenous TCRs in CD8+ NY-ESO-1c259T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1c259T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects.