Adoptive transfer of autologous Epstein-Barr virus-specific cytotoxic T cells for nasopharyngeal carcinoma

Tumor cells from NPC patients are regularly and latently infected with EBV. To examine whether the virus serves as target for immune intervention of t he cancer, we determined levels of EBV-specific CTLp in peripheral blood fr om NPC patients, long-term survivors of the cancer and healthy subjects. CT Lp levels of test subjects varied between 3-3,000/10(6) PBMCs. The plasma E BV burden increased when the CTLp level fell below 150, whereas the EBV bur den of PBMCs was not correlated with CTLp level. Compared with healthy carr iers, CTLp levels of patients were lower and varied over a wider range, bet ween 3-1,500/10(6) PBMCs. The quantitative immune deficit was probably attr ibuted to the tumor because, first, CTLp in survivors was restored to level s similar to those in healthy carriers after the tumor had been successfull y treated. Second, the CTLp level changed as disease progressed, being lowe r in local disease, increased in locoregional disease and decreased again w hen the tumor metastasized. Based on these findings, 4 patients with advanc ed disease were infused with 5 x 10(7)-3 x 10(8) autologous EBV CTLs. The t reatment was safe and unaccompanied by inflammatory or other complications, but whether it improved tumor control could not be discerned from the larg e tumor bulk. Nevertheless, the treatment regularly increased CTLp levels o f patients, maintained it at higher levels for protracted periods and, in 3 patients, restored host surveillance of EBV replication, reducing the plas ma EBV burden. Taken together, these results provided a rationale to furthe r explore EBV as a target of immune intervention of NPC. (C) 2001 Wiley-Lis s, Inc.