Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo.
Lentivirally engineered dendritic cells activate AFP-specific T cells which inhibit hepatocellular carcinoma growth in vitro and in vivo.
复制标题
DOI：
10.3892/ijo.2011.1004
复制
发表时间：
2011-07
影响因子：
5.2
通讯作者：
Wu M
中科院分区：
文献类型：
--
作者：
Liu Y;Butterfield LH;Fu X;Song Z;Zhang X;Lu C;Ding G;Wu M
甲胎蛋白（AFP）是肝细胞癌（HCC）的肿瘤相关抗原，是HCC的既定生物标志物。在这项研究中，我们创建了一个慢病毒表达AFP抗原，并研究了AFP特异性的CD 8 + T细胞的抗肿瘤活性，有和没有CD 4 + T细胞，这是激活的AFP肽脉冲或Lenti-AFP工程化的DC在体外和体内。AFP特异性T细胞能有效杀伤HepG 2肝癌细胞，并产生IL-2、IFN-γ、TNF-α、穿孔素和颗粒酶B，而IL-10（T细胞活化的负调节因子）的产生极少。两种策略都激活了AFP特异性T细胞，但慢病毒策略在几项措施上更上级。数据还支持CD 4 + T细胞在支持抗肿瘤活性方面的影响。异种移植肝癌肿瘤模型的体内研究还表明，AFP特异性T细胞可以显着抑制荷瘤裸小鼠肝癌肿瘤的形成和发病率，并调节相关细胞因子和抗肿瘤分子的血清水平。与人体外T细胞培养物平行，体内模型证明了Lenti-AFP-DC的上级抗肿瘤作用和Th 1-偏移。这项研究支持了基于全长抗原慢病毒的DC疫苗策略优于肽的优势，并为基于DC的疫苗的设计提供了新的见解。
Alpha-fetoprotein (AFP), a tumor-associated antigen for hepatocellular carcinoma (HCC), is an established biomarker for HCC. In this study, we created a lentivirus expressing the AFP antigen and investigated the antitumor activity of AFP-specific CD8+ T cells, with and without CD4+ T cells, which were activated by either AFP peptide-pulsed or Lenti-AFP-engineered DC in vitro and in vivo. AFP-specific T cells could efficiently kill HepG2 HCC cells, and produced IL-2, IFN-γ, TNF-α, perforin and granzyme B, with minimal production of IL-10 (a negative regulator of T cell activation). Both strategies activated AFP-specific T cells, but the lentiviral strategy was superior by several measures. Data also support an impact of CD4+ T cells in supporting anti-tumor activity. In vivo studies in a xenograft HCC tumor model also showed that AFP-specific T cells could markedly suppress HCC tumor formation and morbidity in tumor-bearing nude mice, as well as regulate serum levels of related cytokines and antitumor molecules. In parallel with human in vitro T cell cultures, the in vivo model demonstrated superior anti-tumor effects and Th1-skewing with Lenti-AFP-DC. This study supports the superiority of a full-length antigen lentivirus-based DC vaccine strategy over peptides, and provides new insight into the design of DC-based vaccines.
登录
查看更多内容
影响因子：
11.5
作者：
Butterfield, LH;Ribas, A;Economou, JS
通讯作者：
Economou, JS
影响因子：
14.5
作者：
Abelev, GI;Eraiser, TL
通讯作者：
Eraiser, TL
影响因子：
5.8
作者：
Butterfield, Lisa H.;Ribas, Antoni;Economou, James S.
通讯作者：
Economou, James S.
影响因子：
2.1
作者：
Fisher, RA;Maroney, TP;Posner, MP
通讯作者：
Posner, MP
影响因子：
3.3
作者：
Mizejewski, Gerald J
通讯作者：
Mizejewski, Gerald J