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

We evaluated the safety and activity of autologous T cells expressing NY-ESO-1 c259 , an affi nity-enhanced T-cell receptor (TCR) recognizing an HLA-A2–restricted NY-ESO-1/LAGE1a—derived peptide, in patients with metastatic synovial sarcoma (NY-ESO-1 c259 T cells). Confi rmed antitumor responses occurred in 50% of patients (6/12) and were characterized by tumor shrinkage over several months. Circulating NY-ESO-1 c259 T cells were present postinfusion in all patients and persisted for at least 6 months in all responders. Most of the infused NY-ESO-1 c259 T cells exhibited an effector memory phenotype following ex vivo expansion, but the persisting pools comprised largely central memory and stem-cell memory subsets, which remained polyfunctional and showed no evidence of T-cell exhaustion despite persistent tumor burdens. Next-generation sequencing of endogenous TCRs in CD8 + NY-ESO-1 c259 T cells revealed clonal diversity without contraction over time. These data suggest that regenerative pools of NY-ESO-1 c259 T cells produced a continuing supply of effector cells to mediate sustained, clinically meaningful antitumor effects.