title: Epstein-Barr virus-specific adoptive immunotherapy for recurrent, metastatic nasopharyngeal carcinoma.
abstract: BACKGROUND
  Early-stage and intermediate-stage nasopharyngeal cancer (NPC) generally carry a good prognosis, but for patients with recurrent, metastatic disease, options are limited. In the current study, the authors present a phase 1/2 study to evaluate the efficacy of Epstein-Barr virus (EBV)-stimulated cytotoxic T-lymphocyte (EBV-CTL) immunotherapy in this patient population.
  
  
  METHODS
  Screening for patients with active, recurrent, metastatic EBV-associated NPC began in February 2007, and the study was closed to accrual in January 2012. After informed consent was obtained, patients had their blood drawn to initiate manufacturing of the EBV-CTL product. During product manufacturing, patients were placed on interim standard-of-care chemotherapy, and only after disease progression on the interim chemotherapy did patients receive investigational immunotherapy. Patients were restaged every 2 months until disease progression and then followed for survival.
  
  
  RESULTS
  A total of 28 patients were enrolled, and 21 patients were treated. There was 1 complete response achieved, and at the time of last follow-up, the patient had been in remission for >8 years since treatment. The median progression-free survival was 2.2 months, and the median overall survival was 16.7 months. Two other patients, after failing EBV-CTL immunotherapy, unexpectedly demonstrated strong responses to the chemotherapy regimens they had previously failed. Patient EBV viral load and EBV-CTL specificity for tumor-associated viral antigens did not appear to correlate with clinical response.
  
  
  CONCLUSIONS
  A durable response was observed with EBV-CTL immunotherapy, but the overall response rate for patients with recurrent, metastatic NPC was low. Further research is necessary to increase the efficacy of EBV-specific immunotherapy in patients with incurable NPC, and to characterize mechanisms for refacilitation to chemotherapy. Cancer 2017;123:2642-50. © 2017 American Cancer Society.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Julian
authors.initials: J
authors.lastname: Huang
authors.affiliation: Infectious Diseases Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Mark
authors.initials: M
authors.lastname: Fogg
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Wirth
authors.affiliation: Cancer Vaccine Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Heather
authors.initials: H
authors.lastname: Daley
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.|Cancer Vaccine Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marshall R
authors.initials: MR
authors.lastname: Posner
authors.affiliation: Infectious Diseases Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.|Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Fred C
authors.initials: FC
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Lorch
mesh_terms: D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy*; D002277:Carcinoma / Q000473:pathology / Q000556:secondary / Q000628:therapy* / Q000821:virology; D018450:Disease Progression; D018572:Disease-Free Survival; D058501:Enzyme-Linked Immunospot Assay; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008113:Liver Neoplasms / Q000556:secondary / Q000628:therapy*; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy* / Q000821:virology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000628:therapy* / Q000821:virology; D010865:Pilot Projects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D055815:Young Adult
keywords: Epstein-Barr virus; adoptive T-cell immunotherapy; clinical trials; nasopharyngeal carcinoma; phase 1/2