title: Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1.
abstract: OBJECTIVE
  Adoptive immunotherapy using tumor-infiltrating lymphocytes represents an effective cancer treatment for patients with metastatic melanoma. The NY-ESO-1 cancer/testis antigen, which is expressed in 80% of patients with synovial cell sarcoma and approximately 25% of patients with melanoma and common epithelial tumors, represents an attractive target for immune-based therapies. The current trial was carried out to evaluate the ability of adoptively transferred autologous T cells transduced with a T-cell receptor (TCR) directed against NY-ESO-1 to mediate tumor regression in patients with metastatic melanoma and synovial cell sarcoma.
  
  
  METHODS
  A clinical trial was performed in patients with metastatic melanoma or metastatic synovial cell sarcoma refractory to all standard treatments. Patients with NY-ESO-1-positive tumors were treated with autologous TCR-transduced T cells plus 720,000 iU/kg of interleukin-2 to tolerance after preparative chemotherapy. Objective clinical responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST).
  
  
  RESULTS
  Objective clinical responses were observed in four of six patients with synovial cell sarcoma and five of 11 patients with melanoma bearing tumors expressing NY-ESO-1. Two of 11 patients with melanoma demonstrated complete regressions that persisted after 1 year. A partial response lasting 18 months was observed in one patient with synovial cell sarcoma.
  
  
  CONCLUSIONS
  These observations indicate that TCR-based gene therapies directed against NY-ESO-1 represent a new and effective therapeutic approach for patients with melanoma and synovial cell sarcoma. To our knowledge, this represents the first demonstration of the successful treatment of a nonmelanoma tumor using TCR-transduced T cells.
authors.affiliation: National Institutes of Health, National Cancer Institute, Surgery Branch, Bethesda, MD 20892-1201, USA. Paul_Robbins@nih.gov
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.forename: Steven A
authors.initials: SA
authors.lastname: Feldman
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.forename: Azam V
authors.initials: AV
authors.lastname: Nahvi
authors.forename: Lee J
authors.initials: LJ
authors.lastname: Helman
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.forename: Chyi-Chia Richard
authors.initials: CC
authors.lastname: Lee
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Levy
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.forename: Mona
authors.initials: M
authors.lastname: El-Gamil
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schwarz
authors.forename: Carolyn
authors.initials: C
authors.lastname: Laurencot
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D044127:Epigenesis, Genetic; D005260:Female; D005818:Genetic Engineering; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D018570:Risk Assessment; D013584:Sarcoma, Synovial / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines