自体肿瘤抗原负载的树突细胞联合细胞因子诱导的杀伤细胞治疗中晚期非小细胞肺癌

Clinical reaserch on DCTAA and CIK from stem in treating patients of moderate and advanced stage lung cancer

目的观察自体肿瘤抗原负载的树突细胞（DcTAA）联合配型脐血来源的细胞因子诱导的杀伤细胞（CIK）免疫联合治疗48例中晚期肺癌的临床疗效。方法采用配型的脐血分离单个核细胞（PBMC），在体外用多种细胞因子[CD3McAb、白细胞介素（IL）-2、肿瘤坏死因子（IFN）-γ、IL-1d等1共同诱导成CIK和树突细胞（DC），经过12～15d诱导扩增后获得CIK细胞，再经严格质控检测合格后，分6次回输患者体内，每疗程回输细胞总数为（5～8）×10^9个。培养的第5天用自体肿瘤抗原负载DC，第8天收获DCTAA，行淋巴结部位皮下注射，观察患者接受治疗后瘤体的大小、临床症状积分、生活质量及免疫学指标、Kamofsky评分、体质量、不良反应等的变化，同时记录患者的生存期。结果48例接受脐血DCTAA-CIK治疗的患者中，完全缓解（CR）＋部分缓解（PR）为37例，总缓解率77．1％。临床症状评分改善率78．9％～84．7％；Kamofsky评分提高率为89．6％（43／48）。1年生存率80．6％。不良反应轻微。DCTAA-CIK细胞治疗患者外周血CD3、CD4T细胞和NK细胞比例均显著提高【（42．21±6．12）％、（24．42±3．01）％、0．99±0．34、（24．98±3．02）％与（71．58±7．64）％、（37．25±2．13）％、1．62±0．45、（35．23±4．11）％]（t值分别为6．34、5．67、0．25、4．43，P值均〈0．01）。结论脐血来源的DCTM．CIK细胞过继性免疫治疗是治疗中晚期肺癌的一种良好的方法，能显著提高患者免疫功能，改善患者临床症状，提高生存质量，延长生存期。

Objective To observe the treatment effects in 48 cases of advanced lung cancer patients , with the immune therapy of the dendritic cells loading of tumor autologous antigen （DCTAA） combining with the cells induced factor of the killer cells （CIK） from the matched umbilical cord blood cells. Methods The peripheral blood mononuclear cell （PBMC） from the matched umbilical cord blood cells was seperated, and induced to CIK and DC with some cytokines in vitro, such as CDzMcAb, IL-2, IFN-γ IL-1α, etc. After 12 to 15 days, the amplified CIK cells obtained were obtained, with the strict quality control, infused the CIK cells to the patients body back in six times, about （5-8）×10^9 CIK cells in each time. In the fifth day of the cultivation, DETAA cells were loaded and DCTAA cells were collected in the eighth day, and then hypodermic injection was done. The patient＂ s general situation after the immune treatment was observed, such as the size of the tumors, clinical symptom score, the quality of life and immune indexes. Karnofsky score, weight, toxic side effects and the patient ＂s survival were also studied. Results In the 48 cases with the DCTAS-CIK treatment, complete remission （CR）, partial remission （PR） was 37 cases, the overall remission rate was 77.1%. The improvement rate of clinical symptom scores was from 78.9 % to 84.7 %, the increasing rate of Karnofsky score was 89.6 % （43/48）. 1-year survival reached to 80.6 %. There were significant difference in little toxic side effects（P 〈 0.01）. The proportion of CD3, CD4 and NK cells in peripheral blood cells increased significantly （P 〈 0.01） after DCTAA-CIK cells treatment [（42.21±6.12）%, （24.42±3.01）%, 0.99±0.34, （24.98±3.02） %; （71.58±7.64） %, （37.25±2.13） %, 1.62±0.45, （35.23±4.11） %] （t = 6.34, 5.67, 0.25, 4.43, P 〈0.01）. Conclusion The DCTAA-CIK immune therapy is benefit for advanced lung cancer, not only improve the immune function but also ameliorate the clinical symptoms.