人甲胎蛋白衍生肽脉冲树突状细胞对小鼠肝细胞癌的抑制作用

[Inhibitory effects of human AFP-derived peptide-pulsed dendritic cells on mouse hepatocellular carcinoma].

作者信息

Pang Xiong-Hao, Chen Min-Shan, Jia Wei-Hua, Zhou Xin-Xi

机构信息

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, P. R. China.

出版信息

Ai Zheng. 2008 Dec;27(12):1233-8.

PMID:19079985

Abstract

BACKGROUND & OBJECTIVE: Alpha-fetoprotein (AFP) is a good candidate antigen for the immunotherapy of hepatocellular carcinoma (HCC). How to overcome the immune tolerance induced by autologous antigen is one of key points for inducing effective antitumor immune reaction. This research was to investigate the effect of human AFP-derived peptide-pulsed dendritic cells (hAFP-DCs) on immunity against mouse HCC.

METHODS

Bone marrow-originated DCs were prepared routinely. The activity of hAFP-DC-stimulated cytotoxic T lymphocyte (CTL) against Hepa1-6 cells was examined by MTT assay. C57BL/6 mice were inoculated subcutaneously with 7 x 10(6) Hepa1-6 cells to develop hepatoma, and received intratumor injection of hAFP-DCs, DCs and PBS, respectively, twice a week. Tumor volume was evaluated and the survival of mice after inoculation was observed.

RESULTS

We successfully prepared DCs from bone marrow of mice. The cytotoxic activity of CTLs stimulated by hAFP-DCs and DCs showed stronger tendency than that of control, but without significance. The mean tumor volume at 31 days after inoculation with Hepa1-6 cells was (195.04+/-155.22) mm3 in hAFP-DCs group, (360.65+/-209.02) mm3 in DCs group and (756.19+/-503.24) mm3 in PBS group. The differences among these three groups were significant (P < 0.001). The survival rate of mice at 40 days after inoculation was 100% in hAFP-DCs group, 90% in DCs group and 50% in PBS group (P=0.008).

CONCLUSION

Human AFP-derived peptide-pulsed DCs can efficiently enhance immunity against HCC in mice.

摘要

背景与目的

甲胎蛋白（AFP）是肝细胞癌（HCC）免疫治疗的良好候选抗原。如何克服自体抗原诱导的免疫耐受是诱导有效抗肿瘤免疫反应的关键点之一。本研究旨在探讨人AFP衍生肽脉冲树突状细胞（hAFP-DCs）对小鼠肝癌免疫的影响。

方法

常规制备骨髓来源的DCs。采用MTT法检测hAFP-DC刺激的细胞毒性T淋巴细胞（CTL）对Hepa1-6细胞的活性。将7×10(6)个Hepa1-6细胞皮下接种于C57BL/6小鼠以诱发肝癌，分别每周两次给予瘤内注射hAFP-DCs、DCs和PBS。评估肿瘤体积并观察接种后小鼠的存活情况。

结果

我们成功从小鼠骨髓制备了DCs。hAFP-DCs和DCs刺激的CTL的细胞毒性活性显示出比对照组更强的趋势，但无统计学意义。接种Hepa1-6细胞后31天，hAFP-DCs组的平均肿瘤体积为（195.04±155.22）mm3，DCs组为（360.65±209.02）mm3，PBS组为（756.19±503.24）mm3。这三组之间的差异具有统计学意义（P<0.001）。接种后40天，hAFP-DCs组小鼠的存活率为100%，DCs组为90%，PBS组为50%（P=0.008）。