Background: We and others have demonstrated that adoptive cell therapy with Epstein-Barr virus (EBV)-specific autologous cytotoxic T lymphocytes (CTLs) may control disease progression in patients with EBV-associated nasopharyngeal carcinoma (NPC). With the aim of favoring in vivo T-cell expansion, we optimized our cell therapy approach by administering higher doses of EBV-specific CTLs, following lymphodepleting chemotherapy. Patients and methods: Eleven patients with EBV-related NPC in whom conventional treatment failed have been enrolled. Patients received nonmyeloablative lymphodepleting chemotherapy consisting of cyclophosphamide and fludarabine. Two doses of autologous EBV-specific CTLs were subsequently infused, 2 weeks apart. Study end points were feasibility and clinical outcome. Results: All patients enrolled completed the treatment and were assessable for analysis. The median dose of CTLs per infusion was 3.7 × 10 8. Therapy was well tolerated, with no severe adverse events ascribable to either chemotherapy or cell therapy. Disease control (defined as either tumor regression or disease stabilization lasting >4 months) was obtained in 6 of 11 patients, in keeping with previously published results. Conclusions: Our data confirm that EBV-specific CTL therapy is safe and associated with antitumor activity in patients with advanced NPC. The use of lymphodepleting chemotherapy before high-dose CTL infusion did not enhance the clinical benefit observed in our previous series.
|Titolo:||T-cell therapy for EBV-associated nasopharyngeal carcinoma : preparative lymphodepleting chemotherapy does not improve clinical results|
|Parole Chiave:||Cell therapy; Cytotoxic T lymphocytes; Epstein-Barr virus; Lymphodepletion; Nasopharyngeal carcinoma; Adult; Aged; Disease Progression; Epstein-Barr Virus Infections; Female; Humans; Immunotherapy, Adoptive; Male; Middle Aged; Nasopharyngeal Neoplasms; T-Lymphocytes, Cytotoxic; Young Adult; Cell- and Tissue-Based Therapy; Lymphocyte Depletion; Oncology; Hematology|
|Settore Scientifico Disciplinare:||Settore MED/06 - Oncologia Medica|
|Data di pubblicazione:||feb-2012|
|Digital Object Identifier (DOI):||10.1093/annonc/mdr134|
|Appare nelle tipologie:||01 - Articolo su periodico|