CTL control of EBV in nasopharyngeal carcinoma (NPC): EBV-specific CTL responses in the blood and tumors of NPC patients and the antigen-processing function of the tumor cells

Undifferentiated nasopharyngeal carcinoma (NPC) is latently infected with E BV and expresses a restricted number of viral proteins. Studies in healthy virus carriers have demonstrated that at least some of these proteins can a ct as targets for HLA class I-restricted CTLs, Therefore we have explored t he possibility of a CTL-based therapy for NPC by characterizing EBV-specifi c CTL responses in 10 newly diagnosed NPC cases and 21 healthy virus carrie rs from Southeast Asia. Using the autologous EBV-transformed lymphoblastoid cell line, virus-specific CTL were reactivated in vitro from PBMC, cloned, and screened for cytotoxicity against target cells expressing individual E BV proteins from recombinant vaccinia vectors. EBV-specific CTLs were ident ified in 6 of 10 patients and 14 of 21 controls and mainly targeted the EBV nuclear Ag 3 (EBNA3) family of viral latent proteins. However, in 3 of 10 patients and 11 of 21 controls, CTLs specific for the NPC-associated protei n LMP2 were also detected, albeit at low frequency. EBV-specific CTLs were detected in tumor biopsy material obtained from 3 of 6 of the patients, ind icating that functional CTL are present at the tumor site, but none was spe cific for tumor-associated viral proteins. To assess the Ag-presenting func tion in NPC me studied two NPC-derived cell lines (C15 and c666.1) and demo nstrated that both were capable of processing and presenting endogenously s ynthesized protein to HLA class I-restricted CTL clones. Overall, our data provide a sound theoretical basis for therapeutic strategies that aim to bo ost or elicit LMP2-specific CTL responses in NPC patients.