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

Cancer Discov. 2018 Aug;8(8):944-957. doi: 10.1158/2159-8290.CD-17-1417. Epub 2018 Jun 11.


We evaluated the 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/LAGE1a-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 postinfusion in all patients and persisted for at least 6 months in all responders. Most of the infused NY-ESO-1c259T 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-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.Significance: Metastatic synovial sarcoma is incurable with standard therapy. We employed engineered T cells targeting NY-ESO-1, and the data suggest that robust, self-regenerating pools of CD8+ NY-ESO-1c259T cells produce a continuing supply of effector cells over several months that mediate clinically meaningful antitumor effects despite prolonged exposure to antigen. Cancer Discov; 8(8); 944-57. ©2018 AACR.See related commentary by Keung and Tawbi, p. 914This article is highlighted in the In This Issue feature, p. 899.

Trial registration: NCT01343043.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Adult
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Humans
  • Male
  • Membrane Proteins / immunology*
  • Middle Aged
  • Neoplasm Metastasis
  • Pilot Projects
  • Receptors, Antigen, T-Cell / metabolism*
  • Sarcoma, Synovial / immunology
  • Sarcoma, Synovial / therapy*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation*
  • Treatment Outcome
  • Young Adult


  • Antigens, Neoplasm
  • CTAG1B protein, human
  • Membrane Proteins
  • Receptors, Antigen, T-Cell

Associated data