title: A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response.
abstract: OBJECTIVE
  Although adoptive cell therapy can be highly effective for the treatment of patients with melanoma, the application of this approach to the treatment of other solid tumors has been limited. The observation that the cancer germline (CG) antigen NY-ESO-1 is expressed in 70% to 80% and in approximately 25% of patients with synovial cell sarcoma and melanoma, respectively, prompted us to perform this first-in-man clinical trial using the adoptive transfer of autologous peripheral blood mononuclear cells that were retrovirally transduced with an NY-ESO-1-reactive T-cell receptor (TCR) to heavily pretreated patients bearing these metastatic cancers.
  
  
  METHODS
  HLA-*0201 patients with metastatic synovial cell sarcoma or melanoma refractory to standard treatments and whose cancers expressed NY-ESO-1 received autologous TCR-transduced T cells following a lymphodepleting preparative chemotherapy. Response rates using Response Evaluation Criteria in Solid Tumors (RECIST), as well as immunologic correlates of response, are presented in this report.
  
  
  RESULTS
  Eleven of 18 patients with NY-ESO-1(+) synovial cell sarcomas (61%) and 11 of 20 patients with NY-ESO-1(+) melanomas (55%) who received autologous T cells transduced with an NY-ESO-1-reactive TCR demonstrated objective clinical responses. The estimated overall 3- and 5-year survival rates for patients with synovial cell sarcoma were 38% and 14%, respectively, whereas the corresponding estimated survival rates for patients with melanoma were both 33%.
  
  
  CONCLUSIONS
  The adoptive transfer of autologous T cells transduced with a retrovirus encoding a TCR against an HLA-A*0201 restricted NY-ESO-1 epitope can be an effective therapy for some patients bearing synovial cell sarcomas and melanomas that are refractory to other treatments.
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland. Paul_Robbins@nih.gov.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Robbins
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Sadik H
authors.initials: SH
authors.lastname: Kassim
authors.affiliation: University of California, Irvine, California.
authors.forename: Thai L N
authors.initials: TL
authors.lastname: Tran
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Crystal
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morgan
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Feldman
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: James C
authors.initials: JC
authors.lastname: Yang
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Dudley
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: John R
authors.initials: JR
authors.lastname: Wunderlich
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Sherry
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Udai S
authors.initials: US
authors.lastname: Kammula
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Marybeth S
authors.initials: MS
authors.lastname: Hughes
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Restifo
authors.affiliation: Laboratory of Pathology, NIH, National Cancer Institute, Bethesda, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: Laboratory of Pathology, NIH, National Cancer Institute, Bethesda, Maryland.
authors.forename: Chyi-Chia R
authors.initials: CC
authors.lastname: Lee
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Yong F
authors.initials: YF
authors.lastname: Li
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Mona
authors.initials: M
authors.lastname: El-Gamil
authors.affiliation: NIH, National Cancer Institute, Surgery Branch, Bethesda, Maryland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D010641:Phenotype; D010865:Pilot Projects; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism*; D013584:Sarcoma, Synovial / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell