Folate-Modified Chitosan Nanoparticles Coated Interferon-Inducible Protein-10 Gene Enhance Cytotoxic T Lymphocytes' Responses to Hepatocellular Carcinoma
Folate-Modified Chitosan Nanoparticles Coated Interferon-Inducible Protein-10 Gene Enhance Cytotoxic T Lymphocytes' Responses to Hepatocellular Carcinoma
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DOI：
10.1166/jbn.2016.2216
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发表时间：
2016-04-01
影响因子：
2.9
通讯作者：
Lu, Xiaoling
中科院分区：
文献类型：
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作者：
Duan, Siliang;Song, Mongkhoune;Lu, Xiaoling
使用肿瘤抗原特异性细胞毒性 T 淋巴细胞 (CTL) 的过继疗法是治疗人类癌症的一种有前景的方法。由于癌症患者的免疫抑制，肿瘤抗原特异性CTL很难到达肿瘤组织。干扰素诱导蛋白10（IP-10）是一种强大的趋化因子，可以有效地将CTL吸引到肿瘤组织并提高其抗肿瘤活性。肿瘤组织中IP-10过度表达的增加可以有效促进过继治疗的疗效。因此，本研究开发了包覆人类 IP-10 基因的叶酸修饰壳聚糖纳米粒子 (FA-CS-hIP-10)。 FA-CS-hIP-10纳米粒子特异性结合肝癌细胞上的叶酸受体并促进IP-10的表达，从而提高pMAGE-A1(278-286)特异性CTL的活性。 FA-CS-hIP-10和pMAGE-A1（278-286）特异性CD8（+）CTL的组合有效增加IFN-γ的分泌，抑制肿瘤生长并延长皮下移植人肝细胞癌裸鼠的生存期。我们的结果表明，这种新型治疗方法背后的机制涉及抑制血管生成和增殖，并促进肿瘤细胞凋亡。我们的研究通过提高肿瘤抗原特异性 CTL 的活性，为治疗人类肝细胞癌提供了一种潜在的新方法。
Adoptive therapy using tumor antigen-specific cytotoxic T lymphocytes (CTLs) is a promising approach for treatment of human cancers. Due to immune suppression in cancer patients, it is difficult for tumor antigen-specific CTLs to arrive at tumor tissues. Interferon-inducible protein-10 (IP-10) is a powerful chemokine that effectively attracts CTLs to tumor tissues and improves their anti-tumor activity. Increase over expression of IP-10 in tumor tissues can efficiently promote efficacy of adoptive therapy. Folate-modified chitosan nanoparticles coating the human IP-10 gene (FA-CS-hIP-10) were therefore developed in this study. The FA-CS-hIP-10 nanoparticles were specifically bound to folate receptors on hepatoma cells and promoted the expression of IP-10, to improve the activity of pMAGE-A1(278-286) specific CTLs. Combination of the FA-CS-hIP-10 and pMAGE-A1(278-286) specific CD8(+) CTLs efficiently increased secretion of IFN-gamma, inhibited tumor growth and extended survival of nude mice with subcutaneously transplanted human hepatocellular carcinoma. Our results demonstrated that the mechanism behind this novel therapeutic approach involved inhibition of angiogenesis and proliferation, and also promoted apoptosis of tumor cells. Our study provides a potentially novel approach for treatment of human hepatocellular carcinoma by improving the activity of tumor antigen-specific CTLs.