309th Hospital of PLA, Beijing 100091, China.
Vaccine. 2011 Apr 18;29(18):3501-6. doi: 10.1016/j.vaccine.2011.02.027. Epub 2011 Feb 23.
Recent evidence demonstrates that PEG10 plays an essential role in hepatocarcinogenesis and development, thus it could be regarded as a therapeutical target for hepatocellular carcinoma (HCC). In addition, transduction with recombinant, replication-defective adenoviral (Ad) vectors encoding tumor associated antigen into dendritic cells (DCs) is an efficient strategy to elicit antigen specific cytotoxic T lymphocytes (CTLs) for cancer therapy. In the present study, DCs were transduced with the PEG10 recombinant adenovirus, and were utilized to elicit CTLs in vitro. Moreover, the Trimera mice were immunized with the transduced DCs to elicit the immune response, the tumor growth and the life span of tumor bearing mice were observed. The results demonstrated that the transduced DCs could effectively induce specific CTL response against HCC without lysing autologous lymphocytes, but also significantly inhibit the tumor growth and prolong the life span of tumor bearing mice. These data suggest that PEG10 recombinant adenovirus transduced DCs can induce anti-tumor immunity against HCC expressing PEG10 in vitro and in vivo. Thus, the transduction of DCs with Ad-PEG10 provides a promising strategy for cancer immunotherapy of HCC.
最近的证据表明,PEG10 在肝癌的发生和发展中起着至关重要的作用,因此它可以被视为肝细胞癌(HCC)的治疗靶点。此外,将编码肿瘤相关抗原的重组、复制缺陷型腺病毒(Ad)载体转导到树突状细胞(DC)中是一种有效的策略,可以引发针对癌症治疗的抗原特异性细胞毒性 T 淋巴细胞(CTL)。在本研究中,用 PEG10 重组腺病毒转导 DC,并在体外诱导 CTL。此外,用转导的 DC 免疫 Trimera 小鼠以引发免疫反应,观察肿瘤生长和荷瘤小鼠的寿命。结果表明,转导的 DC 可以有效地诱导针对 HCC 的特异性 CTL 反应,而不会裂解自身淋巴细胞,还可以显著抑制肿瘤生长并延长荷瘤小鼠的寿命。这些数据表明,PEG10 重组腺病毒转导的 DC 可以在体外和体内诱导针对表达 PEG10 的 HCC 的抗肿瘤免疫。因此,用 Ad-PEG10 转导 DC 为 HCC 的癌症免疫治疗提供了一种有前途的策略。