專題討論2:鼻咽癌之預防可用EBV疫苗來達成嗎?
Could EBV Vaccine be Used to Prevent NPC Occurrence ?

S2-1
研發鼻咽癌之DNA疫苗
Development of DNA Vaccines for Nasopharyngeal Carcinoma
婁培人
台大醫院耳鼻喉部

  Cancer vaccine targeting tumor antigens has attracted much attention in recent years because of its higher specificity and less toxicity than traditional modalities such as radiotherapy and chemotherapy. In nasopharyngeal carcinoma (NPC), EB virus nuclear antigen 1 (EBNA1), latent membrane protein 1 (LMP1), and LMP2 offer the best opportunity for specific targeting since these are the only EBV proteins expressed in this malignancy. This is particular so in the case of immunotherapy since defined CD4+ and CD8+ T-cell determinants in each of these proteins have been defined. Recent studies have provided some encouragement that immunotherapeutic intervention may be a realistic treatment option for NPC.

  In addition to the passive immunization approaches for cancer treatment, active immunization by vaccines has also been investigated. Among the various vaccine strategies currently being studied, DNA vaccination possesses many potential advantages over other vaccine strategies and its efficacy has been successfully observed in murine settings. DNA vaccines employ genes encoding proteins of interest, rather than using the proteins themselves and represent a novel means of expressing antigens in vivo for producing both humoral and cellular immune responses.

  In this talk, I will present our preliminary experience in the development of DNA vaccines targeting the LMP-1-specific tumors mimicking NPC. This vaccination strategy is effective in the prevention of tumor growth in vivo. LMP-1 DNA vaccine was given to mice once per week for 3 weeks and then the mice were challenged with LMP-1-positive syngeneic tumor cells. All mice in the vaccine group were tumor-free 2 months after tumor challenge, whilst mice in the control group grew tumors within 2 weeks. Although LMP-1 DNA vaccine significantly protect mice from LMP-1-positive tumors, it could be difficult to translate this result to the clinical setting because immune responses induced by DNA vaccine in humans are generally weak. However, improvement of the vaccine and delivery system design to induce robust immune response by DNA vaccination may have great potential to serve as an efficient vaccine strategy for NPC in humans.