热休克蛋白-多肽复合物/树突状细胞疫苗的研究

Research of GP96-peptide complex dendritic cells tumor vaccince in vivo

目的 探讨从肺癌组织中提取的热休克蛋白GP96 多肽复合物 (GP96)负载树突状细胞 (DC)疫苗在小鼠体内的抗肿瘤作用。方法 自小鼠肺腺癌LA795肿瘤组织中提取GP96,自615小鼠外周血中提取单个核细胞体外培养DC ,共孵育制备疫苗 ,分别以GP96(5 μg/只 )、DC(5×10 5个 /只 )和GP96/DC(DC5× 10 5个 /只 ,培养时加入 5 μgGP96)免疫小鼠后接种肿瘤 ,与未免疫组比较成瘤率、肿瘤体积及生存时间。同时以联合免疫缺陷小鼠 (SCID )进行类似实验 ,肿瘤组织为人肺腺癌PAa ,DC来源于人外周血 ,分组剂量同上。结果 615组小鼠成瘤率分别为 10 0 %、10 0 %、10 0 %和 75 % ,肿瘤体积为 (6.46± 1.47)cm3 ,(0 .70± 0 .62 )cm3 ,(0 .64± 0 .49)cm3 和(0 .3 2± 0 .3 0 )cm3 ,生存时间为 5 2、5 1.5、5 8.5和 77d ,SCID组小鼠成瘤率分别为 10 0 %、10 0 %、10 0 %和 87.5 % ,肿瘤体积为 (0 .75± 0 .3 0 )cm3 ,(0 .17± 0 .0 6)cm3 ,(0 .15± 0 .0 8)cm3 和 (0 .0 8±0 .0 3 )cm3 ,生存时间为 3 7、5 2、5 2 .5和 77d。结论 GP96/DC疫苗有更明显的抑制肿瘤生长的作用。

Objective To investigate the antitumor effect of dendritic cells (DC) combined with heat shock protein Gp96 polypeptide complex derived from lung cancer tissue in vivo.Methods The heat shock protein polypeptide complex were acquired from LA795 adenocarcinima.Mononuclear cells of mice were cultured to produce plenty of DC,and then bound with heat shock protein in vitro to make GP96/DC tumor vaccince.After immunotherapy of 615 mice with GP96,DC and GP96/DC vaccine (5 μg GP96+5×10 5 DC) respectively,they were inoculated with tumor tissue.The progression of tumor and life span of mice were tested.The same progamm was did in SCID mice.Results In the rate of tumr formation was 100%,100%,100% and 75%,the tumor volume was (6.46± 1.47) cm 3, (0.70± 0.62) cm 3, (0.64± 0.49) cm 3 and (0.32± 0.30) cm 3,and the life span was 52 days, 51.5 days, 58.5 days and 77 days resepctively,While in SCID mice,the rate of tumr formation was 100%,100%,100% and 87.5%,the tumor volume was (0.75± 0.30) cm 3, (0.17± 0.06) cm 3, (0.15± 0.08) cm 3 and (0.08± 0.03) cm 3,and the life span was 37 days,52 days,52.5 days and 77 days respectively.Conclusion GP96 polypeptide complex in combination with DC as tumor vaccine can induce effectively antitumor response in vivo.