树突状细胞活化TCR基因转染记忆性T细胞联合化疗治疗EGFR-TKI耐药性晚期非小细胞肺癌的疗效与安全性  

Efficacy and safety of combining infusion of antigen-activated,TCR gene-transfected memory T cells combined with chemotherapy for treating advanced non-small cell lung cancer resistant to EGFR-TKIs

作　　者：江冠铭[1] 袁领勤[2] 贾筠[1] 林顺欢[1] 蔡彦敏[1] 刘淳[1] 吴依芬[1] 王在国[3] 黄树林[4] 

机构地区：[1]东莞市人民医院肿瘤中心肿瘤内科,广东东莞523018 [2]东莞市人民医院肿瘤中心乳腺科,广东东莞523018 [3]东莞市人民医院肿瘤中心肿瘤外科,广东东莞523018 [4]广东药学院生命科学与生物制药学院,广州510006

出　　处：《中国癌症防治杂志》2014年第2期167-171,共5页CHINESE JOURNAL OF ONCOLOGY PREVENTION AND TREATMENT

基　　金：东莞市医疗卫生科技计划基金重点资助项目(201110515000370)

摘　　要：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<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。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.

关 键 词：肺肿瘤 表皮生长因子受体-络氨酸激酶抑制剂 培美曲塞 顺铂 树突状细胞 TCR基因 细胞因子诱导的杀伤细胞 

分 类 号：R734.2[医药卫生—肿瘤]