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The Journal of Immunology, 2000, 165: 573-582.
Copyright © 2000 by The American Association of Immunologists

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 Cells1

Steven P. Lee2,*, Anthony T. C. Chan{dagger}, Siu-Tim Cheung3,{ddagger}, Wendy A. Thomas*, Debbie CroomCarter*, Chris W. Dawson*, Ching-Hwa Tsai§, Sing-Fai Leung{dagger}, Philip J. Johnson{dagger} and Dolly P. Huang{ddagger}

* CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, United Kingdom; Departments of {dagger} Clinical Oncology and {ddagger} Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, People’s Republic of China; § Graduate Institute of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China

Undifferentiated nasopharyngeal carcinoma (NPC) is latently infected with EBV and expresses a restricted number of viral proteins. Studies in healthy virus carriers have demonstrated that at least some of these proteins can act as targets for HLA class I-restricted CTLs. Therefore we have explored the possibility of a CTL-based therapy for NPC by characterizing EBV-specific CTL responses in 10 newly diagnosed NPC cases and 21 healthy virus carriers 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 EBV proteins from recombinant vaccinia vectors. EBV-specific CTLs were identified 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 protein 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, indicating that functional CTL are present at the tumor site, but none was specific for tumor-associated viral proteins. To assess the Ag-presenting function in NPC we studied two NPC-derived cell lines (C15 and c666.1) and demonstrated that both were capable of processing and presenting endogenously synthesized protein to HLA class I-restricted CTL clones. Overall, our data provide a sound theoretical basis for therapeutic strategies that aim to boost or elicit LMP2-specific CTL responses in NPC patients.




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