自体组织抗原负载的树突状细胞对胃癌患者的临床疗效和安全性评估

目的 探讨自体组织抗原联合负载自体树突状细胞(dendritic cells,DC)治疗中老年胃癌的安全性和近期临床疗效。 方法 术中采集20例胃癌患者新鲜肿瘤组织样本，制备成单细胞悬液，经热休克凋亡处理，最终制备成肿瘤抗原，-80℃保存备用。分离20例胃癌患者外周血单核细胞，加入重组人粒细胞－巨噬细胞集落刺激因子(rhGM-CSF)和重组白介素(rhIL)-4诱导成DC,采用自体肿瘤抗原负载DC，1个治疗周期后观察患者的免疫应答与近期临床反应。 结果 治疗过程中未出现不良反应；2次DC注射后患者外周血清中白介素(IL)-2[治疗前平均(46.0±20.3)ng/L，治疗后(85.5±33.3)ng/L]、IL-12[治疗前平均(42.8±13.6)ng/L，治疗后(86.3±33.9)ng/L]和IFN-γ[治疗前平均(39.6±34.3)ng/L,治疗后(82.5±34.8) ng/L]水平呈上升趋势(P＜0.05)；迟发型超敏反应(DTH)试验阳性率为50％(5/10),抗原特异性CD8+ IFN-γ+细胞比例明显增加者5/10(P＜0.01)；1例患者腹膜后淋巴结肿大消失,5例(5/15)癌胚抗原(CEA)下降,8例(8/15)CEA平稳，2例(2/15)上升。 结论自体组织抗原负载自体DC免疫治疗方法可明显改善胃癌患者非特异免疫功能，有效激发特异性T细胞免疫应答，控制并缓解病情，是胃癌一种安全有效的治疗手段。

The dendritic cells loaded with autologous tumor antigen in treatment of elderly patients with gastric cancer:a clinical efficacy and safety evaluation

Objective To evaluate clinical safety and efficacy of autologous tissue antigens loaded dendritic cells (DC)in the treatment of elderly patients with gastric cancer.Methods Fresh tumor cells were isolated from surgical specimens in twenty patients with gastric cancer. Single cell suspensions were obtained and induced to apoptosis by heat shock. The apoptotic tumor cells were frozen before use. Peripheral blood mononuclear cells were isolated and cultured with recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were loaded with apoptotic tumor cells. The immunological and clinical responses were examined after the final vaccination. Results Vaccination of dendritic cells was well tolerated and no toxicity was observed. The cytokine levels in serum such as IL-2(46 pg/mg vs 89 pg/mg), IL-12(44 pg/mg vs. 86 pg/mg) and IFN-γ(38 pg/mg vs. 82 pg/mg) were increased after vaccinations as compared with pretherapy. DTH test were positive in five patients (5/10). The antigen special cells for CD8+/ IFN-γ+ were increased in five patients(5/10). The size of retroperitoneal lymph node of one patient was reduced. The tumor marker CEA level were decreased in five patients, stable in eight patient and increased in two patients.Conclusions Autologous DC vaccines loaded with autologous tumor antigens could improve function of non specific immunity and elicit specific T cells immunologic response and is one of safe and effective treatments for gastric cancer.