title: Adoptive transfer of allogeneic Epstein-Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boosts LMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma.
abstract: BACKGROUND
  The outcome of patients with nasopharyngeal carcinoma (NPC) presenting as advanced-stage disease or failing conventional radio-chemotherapy is poor. Thus, additional forms of effective, low-toxicity treatment are warranted to improve NPC prognosis. Since NPC is almost universally associated with Epstein-Barr virus (EBV), cellular immunotherapy with EBV-specific cytotoxic T lymphocytes (CTLs) may prove a successful treatment strategy. Patient and methods A patient with relapsed NPC, refractory to conventional treatments, received salvage adoptive immunotherapy with EBV-specific CTLs reactivated ex vivo from a human leukocyte antigen-identical sibling. EBV-specific immunity, as well as T-cell repertoire in the tumor, before and after immunotherapy, was evaluated.
  
  
  RESULTS
  CTL transfer was well tolerated, and a temporary stabilization of disease was obtained. Moreover, notwithstanding the short in-vivo duration of allogeneic CTLs, immunotherapy induced a marked increase of endogenous tumor-infiltrating CD8+ T lymphocytes, and a long-term increase of latent membrane protein 2-specific immunity.
  
  
  CONCLUSIONS
  Preliminary data obtained in this patient indicate that EBV-specific CTLs are safe, may exert specific killing of NPC tumor cells in vitro, and induce antitumor effect in vivo.
authors.affiliation: Laboratory of Transplant Immunology and Pediatric Hematology/Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy. pcomoli@smatteo.pv.it
authors.forename: P
authors.initials: P
authors.lastname: Comoli
authors.forename: R
authors.initials: R
authors.lastname: De Palma
authors.forename: S
authors.initials: S
authors.lastname: Siena
authors.forename: A
authors.initials: A
authors.lastname: Nocera
authors.forename: S
authors.initials: S
authors.lastname: Basso
authors.forename: F
authors.initials: F
authors.lastname: Del Galdo
authors.forename: R
authors.initials: R
authors.lastname: Schiavo
authors.forename: O
authors.initials: O
authors.lastname: Carminati
authors.forename: A
authors.initials: A
authors.lastname: Tagliamacco
authors.forename: G F
authors.initials: GF
authors.lastname: Abbate
authors.forename: F
authors.initials: F
authors.lastname: Locatelli
authors.forename: R
authors.initials: R
authors.lastname: Maccario
authors.forename: P
authors.initials: P
authors.lastname: Pedrazzoli
mesh_terms: D000328:Adult; D000956:Antigens, Viral / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D008297:Male; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology* / Q000473:pathology / Q000628:therapy* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000276:immunology*; D017735:Virus Latency
chemical_list: D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins