【摘要】 目的研究自体肝癌肿瘤浸润淋巴细胞(TIL)体外扩增后回输联合抗PD-1单抗治疗晚期肝癌的安全性及有效性。方法选择肝癌术后复发不能再次根治切除或伴有肝外转移的肝癌病人为研究对象。从切除的肿瘤中分离TIL、或从腹腔镜下获取的肿瘤组织中获取TIL,体外分离扩增,当TIL扩增至少达到2×109个时进行回输,输注后联用抗PD-1单抗,并持续给予白细胞介素(IL)-2注射维持TIL活性,观察不良反应及初步疗效。结果对4例晚期肝癌病人成功分离、扩增及回输TIL。4例病人均显示出良好的耐受性,不良反应小。目前中位随访7.5个月,2例病人存活,生存的病人中1例肺转移灶消失,另1例肾上腺转移灶部分坏死。另2例最早入组的肝癌病人因入组时肿瘤负荷较大,分期较晚,疾病进展死亡,生存时间分别为3个月和6个月。结论自体TIL体外扩增回输联合抗PD-1单抗治疗晚期肝癌病人安全可行,初步观察其有效,长期疗效值得深入研究。TIL体外扩增回输联合抗PD-1单抗治疗可能成为一种治疗肝癌的新方法。更多还原

【Abstract】 Objective To study the safety and efficacy of clinical application of autologous tumor infiltrating lymphocytes( TIL) after in vitro amplification,in combination with anti-PD-1 monoclonal antibody for the treatment of advanced hepatocellular carcinoma( HCC). Methods The patients with postoperative recurrence or extrahepatic metastasis that are not operable were selected for the study. TIL were isolated from the tumor samples obtained through local resection under laparoscopy,and TIL were amplified up to 2 × 109 cells and administered intravenously to the patients. After TIL infusion,anti-PD-1 monoclonal antibody injection was followed every 21 days,and IL-2 was continuously injected to maintain the activity of TIL for two weeks,and the adverse effects and treatment efficacy were evaluated. Results TIL were successfully isolated,amplified and administered in 4 patients with advanced liver cancers. All 4 patients showed good tolerance and minor adverse effects. At present,the median follow-up period was 7. 5 months,2 patients are under observation,one with lung metastatic lesion disappearing and the another with adrenal metastatic lesion partially necrotizing. The other 2 patients died due to high tumor load and advanced stage of tumor,and their survival time was 3 months and 6 months,respectively. Conclusion TIL amplification and reinfusion combined with anti-PD-1 monoclonal antibody is safe and feasible in the treatment of advanced HCC,and the long-term efficacy requires further studies. Application of TIL amplified in vitro combined with anti-PD-1 monoclonal antibody is likely a hopeful new therapy for HCC.更多还原