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

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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 cytokine-induced killer cells (CIK) derived from dendritic cell-based vaccine (DCA) combined with umbilical cord blood-derived cytokine-induced killer cells (CIK). Clinical efficacy of immunotherapy for 48 patients with advanced lung cancer. Methods Mononuclear cells (PBMCs) were isolated from umbilical cord blood and used to induce CIK and DC in vitro using multiple cytokines (CD3McAb, IL-2, IFN-γ, IL-1α, etc.). After 12-15 days, CIK and DC were induced. After induction of amplification, CIK cells were obtained, and after passing the stringent quality control test, they were returned to the patient in 6 sessions. The total number of returned cells per treatment was (5-8)×10-9. On the fifth day of culture, DCs were loaded with autologous tumor antigen, and on the 8th day, tumor-antigen-loaded DC-TAA lymph nodes were injected subcutaneously. The size, clinical symptom scores, quality of life, and immunology of the patients after treatment were observed. Changes in indicators, Karnofsky scores, weight, adverse reactions, etc., while recording the patient’s life span. Results Of the 48 patients who received cord blood DC-TAA-CIK, CR+PR was 37. The total response rate was 77.1%. The improvement rate of clinical symptom scores was 78.9%-84.7%; the improvement rate of quality of life was 89.6%. The one-year survival period reaches 80.6%. The adverse reaction was slight. The ratio of CD3, CD4 T cells and NK cells in peripheral blood of patients treated with DCs (TAA)-CIK cells was significantly increased, and the difference was statistically significant (P<0.01). Conclusion Adoptive immunotherapy with DC-TAA-CIK cells derived from umbilical cord blood is a good treatment for advanced lung cancer. It can significantly improve the immune function of patients, improve clinical symptoms, improve the quality of life, and prolong survival.
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