EBV-SPECIFIC CYTOTOXIC T-LYMPHOCYTES FOR EBV-POSITIVE NASOPHARYNGEAL CANCER PTS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。鼻咽癌的常规治疗经常失败，并伴有严重的长期副作用。由于几乎所有未分化的npc都与eb病毒（EBV）相关，因此这种肿瘤是针对肿瘤相关病毒抗原的细胞免疫治疗的一个有吸引力的候选肿瘤。我们现在证明ebv特异性细胞毒性t细胞（CTL）系可以很容易地从NPC个体中产生，尽管患者先前暴露于化疗/放疗。共有10例诊断为晚期鼻咽癌的患者接受了自体ctl治疗。所有患者都能耐受ctl，尽管其中一名患者在原有疾病部位出现肿胀增加。输注后19至27个月，4例局部晚期疾病缓解患者仍无疾病。在治疗前的6例难治性疾病患者中，2例完全缓解，治疗后11至23个月仍处于缓解期；我的部分缓解持续了12个月；1例病情稳定14个月以上；2号没有回应。这些结果表明，ebv特异性ctl治疗晚期鼻咽癌患者是可行的，似乎是安全的，并且与显著的抗肿瘤活性相关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Conventional treatment for nasopharyngeal carcinoma (NPC) frequently fails and is accompanied by severe long-term side effects. Since virtually all undifferentiated NPCs are associated with Epstein-Barr virus (EBV), this tumor is an attractive candidate for cellular immunotherapy targeted against tumor-associated viral antigens. We now demonstrate that EBV-specific cytotoxic T-cell (CTL) lines can readily be generated from individuals with NPC, notwithstanding the patients' prior exposure to chemotherapy/radiation. A total of 10 patients diagnosed with advanced NPC were treated with autologous CTLs. All patients tolerated the CTLs, although one developed increased swelling at the site of pre-existing disease. At 19 to 27 months after infusion, 4 patients treated in remission from locally advanced disease remain disease free. Of 6 patients with refractory disease prior to treatment, 2 had complete responses, and remain in remission over 11 to 23 months after treatment; 1 had a partial remission that persisted for 12 months; 1 has had stable disease for more than 14 months; and 2 had no response. These results demonstrate that administration of EBV-specific CTLs to patients with advanced NPC is feasible, appears to be safe, and can be associated with significant antitumor activity.