Quantitative study of cytotoxic T-lymphocyte immunotherapy for nasopharyngeal carcinoma

The concentration of epidermal growth factor receptor (EGFR) in the tumor cell cytomembranes increases after CTL is added. Concurrently, there is a marked downward trend of the phosphorylated transforming growth factor-α (TGFα)-EGFR complex in the tumor cell cytomembranes, which indicates restriction of tumor growth after CTL immunotherapy. The relationships among the time of addition of CTL, the amount of CTL added, different CTL specificities for LMP2 and the increment rate k of the total number of tumor cells were evaluated.The simulation results quantify the relationships among treatment time-points, amount of CTL added, and the corresponding therapeutic effect of immunotherapy for NPC.Epstein-Barr virus is present in virtually all poorly-differentiated and undifferentiated nasopharyngeal carcinomas (NPC) and the viral antigens expressed by the tumor provide potential targets for immunotherapy [1]. NPCs only express a restricted set of less immunogenic viral antigens (latency type II), namely EBNA-1, LMP-1 and LMP-2. The most likely target antigen for a CD8+ cytotoxic T-lymphocyte (CTL)-based therapy is LMP-2.A pilot study using adoptive T cell therapy to treat NPC was reported in 2001 [2]. Autologous EBV-transformed B-lymphoblastoid cell line (LCL)-reactivated T cells were generated in vitro and used to treat four advanced cases of NPC. The use of autologous EBV-specific CTL for NPC has since been evaluated in two clinical trials [3,4]. Both studies demonstrated that autologous EBV-specific CTL is safe, induces LMP-2-specific immune responses, and is associated with an objective response and control of disease in advanced NPC. However, the EBV-specific CTL lines in these studies were generated by stimulation with EBV-LCL, which favored the outgrowth of CTL responses to the immunodominant EBNA-3 proteins rather than the subdominant EBV proteins LMP-1 and LMP-2 expressed in NPC. The anti-tumor response could be further enhanced by strategies that increase the spe