新型全细胞瘤苗对荷肝癌小鼠的主动免疫治疗

Active specific immunotherapy of mice bearing liver cancer using novel whole cell tumor vaccine

目的 建立小鼠肝脏种植性肝癌模型，评价添加新型佐剂的全细胞肿瘤瘤苗的治疗效果，包括免疫学参数及小鼠存活期，探讨该肿瘤瘤苗的作用机制。方法Ｂａｌｂ／ｃ小鼠肝脏成功接种肿瘤后，分成４组，各组行不同的治疗。第１组单纯切除肿瘤，不做免疫治疗；第Ⅱ组切除肿瘤，用新型细胞瘤苗进行免疫治疗；第Ⅲ组不切除肿瘤，用新型瘤苗进行免疫治疗；第Ⅳ组为对照组，只进行开腹、关腹。第２８天处死各组半数小鼠，取血检测血清中ＩＬ－１０和ＩＦＮ－γ的水平；取脾用ＦＡＣＳ检测ＣＤ４／ＣＤ8 和 ＩＦＮ－γ／ＩＬ－１０双阳性细胞的比例。各组所余小鼠继续饲养，鹏存活期。结果第腴血清ＩＦＮ-γ的水平较其余组明显升高（ｐ＜０.０１）；血清 ＩＬ－１０的水平较其他组明显降低（ｐ＜０．０１）；ＣＤ８＋／ＩＦＮ－γ+细胞的比例明显高于其他各组（ｐ＜０.０１）； ＣＤ８+／ＩＬ－１０+细胞的比例明显低于其他各组（ｐ＜０.０１）；ＣＤ４＋／ＩＦＮ-γ+细胞的比例明显高于靴各组（ｐ＜０.０１）；ＣＤ４＋／ＩＬ－１０＋细胞的比例明显低于其他各组（ｐ＜０.０１）．同时，第Ⅱ组荷瘤小鼠的生存期亦有明显延长。各组肺或淋巴结转移无统计学意义。

Aim To evaluate the therapeutic efficacy of a novel ho- mologous tumor vaccine with the addition of novel adjuvant through the medium of model established by implanting homologous liver cancer into Balb/c mice and explore the mechanism of the vaccine. Methods After the tumor were successfully implanted in the liver, the Bulb/c mice were divided into 4 groups randomly. Tumor resec- tion was performed in group I without immunotherapy. Mice in group II received novel homologous tumor vaccine after tumors were removed. Tumor resection was not performed in group Ⅲ, only vac- cinating homologous tumor cell vaccine. The Ⅳ group was control group. Half of the mice in every group was killed on 28th day to test levels of IL-l0, serum IFN-γ and the alteration of proportions of CD8^+/IFN-γ^+ ,CD8^+/IL-l0^+ cells, CD4^+/IFN-γ^+ and CD4^+/ IL- 10^+ cells in spleen. Other mice in every group were fed contin- ously to calculate survival time. Results Level of serum IFN-γ in group Ⅱ were increased obviously as compared with other groups (p <0. 01). On the contrary, level of serum IL-l0 of this group was obviously lower than that in other groups (p <0. 01). Also, in this group, the proportions of CD8^+ /IL-γ^+ and CD4 ^+/IFN~γ + cells were higher than those in other groups (p <0. 01); while propor- tions of CD8 ^+/IL-l0^+ and CD4^+ /IL-10 ^+ cells decreased obviously as compared with other groups(p <0.01). The survival time of the mice in group Ⅱ were prolonged to 42 days. Metastasis of tumor was found in other groups except group Ⅱ, but there is no significant difference by comparison with each other. Conclusions The novel homologous tumor vaccine can elicit specific cellular immune re- sponse and improve the host's antitumor immunity. This novel ho- mologous tumor vaccine has the advantages of simple manipulation and inexpensive. Therefore, it is suitable for extended application.