CAJ | 학술논문

目的：观察负载抗原树突状细胞（dendritic cell，DC）活化TCR基因转染记忆性T细胞联合培美曲塞、顺铂治疗表皮生长因子受体络氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitors，EGFR-TKI）耐药性晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的临床疗效及毒副反应。方法41例EGFR-TKI耐药性晚期NSCLC患者分为联合治疗组和化疗组。联合治疗组21例，化疗前两天抽取患者外周血液进行DC活化T细胞增殖，化疗后14 d静脉回输该细胞，以培美曲塞500 mg/m2静脉滴注，d1；顺铂75 mg/m2静脉滴注，d1。每3周重复1次。化疗组20例，以培美曲塞500 mg/m2静脉滴注，d1；顺铂75 mg/m2，静脉滴注，d1。每3周重复1次。观察两组近期疗效、患者免疫功能的变化、生活质量和毒副反应等。结果联合治疗组患者治疗后外周血液中CD3+、CD4+、CD8+、CD4+/CD8+、CD95+和CD122+明显增加，与治疗前比较差异有统计学意义（P均约0.05）。联合治疗组和化疗组有效率分别为33.33%和30.00%（P>0.05），疾病控制率分别为76.19%和60.00%（P<0.05）。中位疾病无进展时间联合治疗组为7.1个月，明显高于化疗组的3.7个月（P<0.05）。联合治疗组患者KPS评分改善率为85.71%，高于化疗组45.00%（P<0.05）。联合治疗组患者粒细胞减少、恶心呕吐和疲乏的发生率分别为46.6%、52.4%和23.8%，明显低于化疗组的75.0%、90.0%和65.0%（P<0.05）。结论负载抗原DC活化TCR基因转染记忆性T细胞联合培美曲塞、顺铂治疗EGFR-TKI耐药性晚期NSCLC的疗效较好，能提高患者免疫功能和改善生活质量，减低化疗毒副反应，安全性较好。
목적：관찰부재항원수돌상세포（dendritic cell，DC）활화TCR기인전염기억성T세포연합배미곡새、순박치료표피생장인자수체락안산격매억제제（epidermal growth factor receptor tyrosine kinase inhibitors，EGFR-TKI）내약성만기비소세포폐암（non-small cell lung cancer，NSCLC）적림상료효급독부반응。방법41례EGFR-TKI내약성만기NSCLC환자분위연합치료조화화료조。연합치료조21례，화료전량천추취환자외주혈액진행DC활화T세포증식，화료후14 d정맥회수해세포，이배미곡새500 mg/m2정맥적주，d1；순박75 mg/m2정맥적주，d1。매3주중복1차。화료조20례，이배미곡새500 mg/m2정맥적주，d1；순박75 mg/m2，정맥적주，d1。매3주중복1차。관찰량조근기료효、환자면역공능적변화、생활질량화독부반응등。결과연합치료조환자치료후외주혈액중CD3+、CD4+、CD8+、CD4+/CD8+、CD95+화CD122+명현증가，여치료전비교차이유통계학의의（P균약0.05）。연합치료조화화료조유효솔분별위33.33%화30.00%（P>0.05），질병공제솔분별위76.19%화60.00%（P<0.05）。중위질병무진전시간연합치료조위7.1개월，명현고우화료조적3.7개월（P<0.05）。연합치료조환자KPS평분개선솔위85.71%，고우화료조45.00%（P<0.05）。연합치료조환자립세포감소、악심구토화피핍적발생솔분별위46.6%、52.4%화23.8%，명현저우화료조적75.0%、90.0%화65.0%（P<0.05）。결론부재항원DC활화TCR기인전염기억성T세포연합배미곡새、순박치료EGFR-TKI내약성만기NSCLC적료효교호，능제고환자면역공능화개선생활질량，감저화료독부반응，안전성교호。
Objective To examine whether infusion of antigen-activated memory T cells transfected with TCR genes alters the clinical efficacy and toxicity of pemetrexed-cisplatin combination chemotherapy to treatin the treatment of advanced non-small cell lung cancer resistant to EGFR-TKIs. Methods A total of 41 patients with non-small cell lung cancer were randomized into a group (n=20)that received standard chemotherapy involving a 3-week regime of pemetrexed (500 mg/m2)and cisplatin (75 mg/m2),or into a group (n=21)that received the same chemotherapy after harvesting,culturing and intravenously infusing DC-activated T cells.Curative effects,immune function,quality of life and adverse reactions were compared between the two treatments. Results Combining infu-sion of DC-activated T cells with chemotherapy significantly increased serum populations of CD3+,CD4+,CD8+,CD95+,and CD122+cells,as well as the CD4+/CD8+ ratio.Combination therapy and standard chemotherapy alone gave similar overall response rates of 33.33%and 30.00%(P>0.05),respectively,but combination therapy led to a significantly higher disease control rate(76.19%vs 60.00%, P<0.05),longer median progression-free survival (7.1 vs 3.7 months,P<0.05),and a higher rate of improvement in KPS(karnofsky performance status)improvement rate (85.71% vs 45.00%,P<0.05).At the same time,combination therapy was associated with much lower rates of neutropenia(46.6% vs 75.0%),nausea(52.4% vs 90.0%)and fatigue(23.8% vs 65.0%,P<0.05). Conclusion Combining infusion of antigen-activated memory T cells with pemetrexed and cisplatin chemotherapy improves therapeutic response and immune function while also reducing side effects when treating patients with advanced non-small cell lung carcinoma resistant to EGFR-TKIs.This promising therapeutic approach should be explored further.