Sun Q F, Zhao X N, Peng C L, Hao Y T, Zhao Y P, Jiang N, Xue H, Guo J Z, Yun C H, Cong B, Zhao X G
Department of Thoracic Surgery, Second Hospital of Shandong University, Jinan, Shandong, P.R. China.
Department of Comprehensive Health Ⅱ, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China.
Oncol Rep. 2015 Nov;34(5):2289-95. doi: 10.3892/or.2015.4231. Epub 2015 Aug 27.
Dendritic cells (DCs) as 'professional' antigen-presenting cells (APCs) initiate and regulate immune responses to various antigens. DC-based vaccines have become a promising modality in cancer immunotherapy. Cytokeratin 19 (CK19) protein is expressed at high levels in lung cancer and many other tumor cells, suggesting CK19 as a potential tumor‑specific target for cancer immune therapy. We constructed a recombinant adenoviral vector containing the CK19 gene (rAd-CK19). DCs transfected with rAd-CK19 were used to vaccinate C57BL/6 mice bearing xenografts derived from Lewis lung carcinoma (LLC) cells. The transfected DCs gave rise to potent CK19-specific cytotoxic T lymphocytes (CTLs) capable of lysing LLC cells. Mice immunized with the rAd‑CK19-DCs exhibited significantly attenuated tumor growth (including tumor volume and weight) when compared to the tumor growth of mice immunized with rAd-c DCs or DCs during the 24-day observation period (P<0.05). The results revealed that the mice vaccinated with the rAd-CK19-DCs exhibited a potent protective and therapeutic antitumor immunity to LLC cells in the subcutaneous model along with an inhibitive effect on tumor growth compared to the mice vaccinated with the rAd-c DCs or DCs alone. The present study proposes a meaningful mode of action utilizing rAd-CK19 DCs in lung cancer immunotherapy.
树突状细胞(DCs)作为“专职”抗原呈递细胞(APCs),启动并调节对各种抗原的免疫反应。基于DC的疫苗已成为癌症免疫治疗中一种有前景的方式。细胞角蛋白19(CK19)蛋白在肺癌和许多其他肿瘤细胞中高水平表达,提示CK19作为癌症免疫治疗的潜在肿瘤特异性靶点。我们构建了一种包含CK19基因的重组腺病毒载体(rAd-CK19)。用rAd-CK19转染的DCs用于给携带源自Lewis肺癌(LLC)细胞异种移植物的C57BL/6小鼠接种疫苗。转染后的DCs产生了能够裂解LLC细胞的强效CK19特异性细胞毒性T淋巴细胞(CTLs)。在24天的观察期内,与用rAd-c DCs或DCs免疫的小鼠的肿瘤生长相比,用rAd-CK19-DCs免疫的小鼠的肿瘤生长(包括肿瘤体积和重量)显著减缓(P<0.05)。结果显示,与用rAd-c DCs或单独的DCs接种疫苗的小鼠相比,用rAd-CK19-DCs接种疫苗的小鼠在皮下模型中对LLC细胞表现出强效的保护性和治疗性抗肿瘤免疫以及对肿瘤生长的抑制作用。本研究提出了一种在肺癌免疫治疗中利用rAd-CK19 DCs的有意义的作用模式。