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

• Published in: Cancer discovery 2018-06, Vol.8 (8), p.944-957
• Main Authors: D'Angelo, Sandra P., Melchiori, Luca, Merchant, Melinda S., Bernstein, Donna, Glod, John, Kaplan, Rosandra, Grupp, Stephan, Tap, William D., Chagin, Karen, Binder, Gwendolyn K., Basu, Samik, Lowther, Daniel E., Wang, Ruoxi, Bath, Natalie, Tipping, Alex, Betts, Gareth, Ramachandran, Indu, Navenot, Jean-Marc, Zhang, Hua, Wells, Daniel K., Winkle, Erin Van, Kari, Gabor, Trivedi, Trupti, Holdich, Tom, Pandite, Lini, Amado, Rafael, Mackall, Crystal L.
• Format: Article
• Language: English
• ISSN: 2159-8274; 2159-8290
• DOI: 10.1158/2159-8290.CD-17-1417

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.