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中国癌症防治杂志

中国癌症防治杂志 ›› 2014, Vol. 6 ›› Issue (2): 167-171.doi: 10.3969/j.issn.1674-5671.2014.02.14

• 转化医学 • 上一篇    下一篇

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

  

  1. 东莞市人民医院肿瘤中心肿瘤内科；乳腺科；肿瘤外科；广东药学院生命科学与生物制药学院 
  • 出版日期:2014-06-25 发布日期:2014-07-08
  • 通讯作者: 贾 筠 E-mail:dgryjy@sina.com
  • 基金资助:

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

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

  • Online:2014-06-25 Published:2014-07-08

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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。

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

Abstract:  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.

Key words: Lung neoplasm, EGFR-TKI, Pemetrexed, Cisplatin, Dendritic cell, TCR gene, Cytokine-induced killer cell