自体肿瘤疫苗主动特异性免疫治疗进展期肿瘤的初步研究

Preliminary study on antitumor effect of active specific immunotherapy with autologous tumor vaccine in post-operative patients with advanced tumors

目的 :探讨自体肿瘤疫苗的作用机制及临床意义。方法 :30例进展期肿瘤病人术后 ,以自体肿瘤疫苗辅助主动免疫治疗。术后第 4周开始接种 (共 4次 ,每次间隔 7～ 10d) ;接种前 3天及 4次接种后 1w ,采集外周血 ,分离单个核细胞 ,测定CD+8 IFN γ+ ,CD+8 IL 10 + 细胞比例及CD+4 IFN γ+ 、CD+4 IL 10 + 细胞比例 ;同时采集血清检测血清IFN γ、IL 10水平 ;用PPD及自体抗瘤抗原做皮肤迟发型过敏反应试验 ,4 8h后测量红斑、硬结大小 (mm)。临床随访。结果 :自体免疫苗治疗后 :①血清IFN γ水平升高 ,高 (5 98± 2 4 0 )pg ml升至 (11 2 0± 4 76 )pg ml;而IL 10水平由 (2 6 0 4± 12 85 )pg ml降至 (8 12± 3 6 9)pg ml,差异有非常显著性 (P <0 0 5 )。②CD+8 IFN γ+ 双阳性细胞比例由 (3 72± 1 5 6 ) %升至 (8 0 1± 2 5 4 ) % ;CD+4 IFN γ+ 双阳性细胞比例由 (4 5 2± 1 0 8) %升至 (7 94± 2 0 6 ) %。差异有非常显著性 (P <0 0 5 )。③治疗前后病人对自体肿瘤抗原的特异性DTH反应明显增强 (P <0 0 1)。④病人耐受性良好 ,无溃疡等严重副作用发生。⑤随访结果显示 :2 2例病人无瘤生存时间超 3年 ,其中部分病人无瘤生存时间超过 5年。结论 :①自体肿瘤疫苗可激发病人特异性细胞介导的免疫反?

Objective:The explore the mechanism of active immunotherapy with autologous tumor vaccine and clinical significance.Methods:30 patients with advanced tumors were enrolled in this study.4 weeks after operation,the patients received vaccinations of autologous tumor vaccine every 7～10 days for 4 times as adjuvant active immunotherapy,3 days before and 7 days after administrations:peripheral blood monuclear cells(PBMC) were isolated to assay the alteration of proportions of CD + 8 IFN γ + and CD + 8 IL 10 +,CD + 4 IFN γ + and CD + 4 IL 10 + cells.Meanwhile,serum IFN γ and IL 10 were measured within 48 hours after the skin tests with PPD and autologous tumor antigen,diameters of erythemas or indurations were observed.The clinical follow up was performed.Results:After active immunotherapy with autologous tumor vaccine.①The serum IFN γ was increased from (5.98±2 40)pg/ml to (11.20±4.76) pg/ml(P<0.05) and the serum IL 10 was decreased from (21.04±12 85)pg/ml to (8.12±3.69)pg/ml (P<0.05).②The proportion of CD + 4 IFN γ + cell was elevated from(4.52±1.08)% to (7.94±2.06)%(P<0 05).③Specific DTH reactions to autologous tumor antigen were enhanced obviously(P<0.01).④The patients tolerated well withous serious side effects such as ulceration.⑤The follow up shows that the disease free interval of 22 patients were more than 3 years,6 of whom were more than 5 years.Conclusion:①The autologous tumor vaccine can elicit specific cellular immune response.②It can improve the host's anti tumor immune response.③It may play an important role in improving life quality survival and prevention of recurrence and metastasis.