树突状细胞瘤苗联合细胞因子诱导的杀伤细胞治疗非小细胞肺癌的疗效观察

Efficacy of DCTAA combined with CIK in treatment of patients with moderate and advanced stage lung cancer

目的观察自体肿瘤抗原负载的树突状细胞(dendritic cell-based vaccine,tumor associated antigen,DC^(TAA))联合配型脐血来源的细胞因子诱导的杀伤细胞(cytokine-induced killer cells,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、IL-2、IFN-γ、IL-1α等)共同诱导成CIK和DC,经过12～15 d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天收获负载肿瘤抗原的DC^(TAA)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、卡氏评分、体重、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DC^(TAA)-CIK治疗的患者中,CR+PR为37例,总缓解率为77.1%。临床症状评分改善率为78.9%～84.7%;生存质量卡氏评分提高率为89.6%。1年生存期达到80.6%。不良反应轻微。DC^(TAA)-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,差异有统计学意义(P<0.01)。结论脐血来源的DC^(TAA)-CIK细胞过继性免疫疗法不失为中晚期肺癌一种良好的治疗方法,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 efficacy in 48 patients with moderate and advanced lung cancer treated by immuno therapy of the dendritic calls loading of tumor autologous antigen （ DCTAA ） combined with the cells induced factor of the killer cells （CIK） from the matched umbilical cord blood cells. Methods The peripheral blood mononuclear cells （PBMC） were separated from the matched um- bilical cord blood cells, induced to CIK and DC with some cytokines in vitro, such as CD3McAb, IL- 2, IFN-γ,IL- 1α, etc. After 12 to 15 days, we obtained the amplified CIK cells and infused the CIK cells back to the patients＇body six times under strict quality con- trol, about 5 -8 ×10^9 CIK cells in each time. On the fifth day of the cultivation, we loaded DC with tumor autologous antigen, obtained DCTAA cells on the eighth day, and then gave a hypodermic injection to lymph nodes. The patient＇s general condition after the immuno- therapy was observed, such as the size of the tumor, clinical symptom score, the quality of life and immune indexes, Kamofsky score, weight, toxic and side effects, and the patient＇s survival was also studied. Results Of the 48 cases undergoing DCTAA - CIK treatment, complete remission（CR） and partial remission （PR） were effected in 37 cases. The overall remission rate was 77.1%. The improvement rate of clinical symptom scores ranged from 78.9% to 84.7%, and the increase rate of Kamofsky score was 89.6%. One - year survival reached 80.6%. Toxic and side effects were trivial with significant difference （P 〈0.01 ）. The proportions of CD3 , CD4 and NK cells in peripheral blood cells increased significantly （P 〈 0.01 ） after DCTAA - CIK cells treatment. Conclusions The DCTAA- CIK immuno therapy is effective for advanced lung cancer by not only improving the immune function but also ameliorating clinical symptoms.