Mol Biol Rep. 2013 Oct;40(10):5615-23. doi: 10.1007/s11033-013-2663-7.
To explore the anti-tumor effect and immune mechanism mediated by a new recombinant adeno-associated virus (rAAV) encoding secondary lymphoid tissue chemokine (SLC) mature peptide gene. AAV Helper-Free system was used for rAAV-SLC package. The anti-tumor effect of SLC was detected by bearing tumor established from Hepal-6 cells both in C57BL/6J and nude mice. Flow cytometry analysis and IHC for Tumor-infiltrating T cells and CD11c+DCs were also investigated to explore the immunological mechanism. rAAV-SLC was successfully packaged in AAV293 cells and transfected Hepal-6 tumor cells at high efficiency. The anti-tumor effect was demonstrated by less tumor weight and longer survival outcome. Coincident with the anti-tumor response, local elaboration of SLC within the tumor bed elicited a heavy infiltration of CD4+, CD8+T cells and CD11c+ dendritic cells into the tumor sites. More importantly, there was higher infiltration of Foxp3+ regulatory T cells (Tregs). Local elaboration of SLC mediated by rAAV-SLC has strong T cell mediated anti-tumor effect. The study also suggested that Tregs in the tumor microenvironment tampered the anti-tumor effect.
探索新型重组腺相关病毒（rAAV）编码二级淋巴组织趋化因子（SLC）成熟肽基因介导的抗肿瘤作用和免疫机制。采用 AAV 无辅助系统包装 rAAV-SLC。通过在 C57BL/6J 和裸鼠中建立来自 Hepal-6 细胞的肿瘤，检测 SLC 的抗肿瘤作用。还通过流式细胞术分析和肿瘤浸润 T 细胞和 CD11c+DCs 的 IHC 来探讨免疫机制。rAAV-SLC 在 AAV293 细胞中成功包装，并高效转染 Hepal-6 肿瘤细胞。通过肿瘤重量减轻和生存时间延长证明了抗肿瘤作用。与抗肿瘤反应一致，肿瘤床内 SLC 的局部表达引起 CD4+、CD8+T 细胞和 CD11c+树突状细胞大量浸润到肿瘤部位。更重要的是，Foxp3+调节性 T 细胞（Tregs）的浸润水平更高。rAAV-SLC 介导的 SLC 局部表达具有强大的 T 细胞介导的抗肿瘤作用。该研究还表明，肿瘤微环境中的 Tregs 干扰了抗肿瘤作用。
