Kulikova E V, Kurilin V V, Shevchenko J A, Obleukhova I A, Khrapov E A, Boyarskikh U A, Filipenko M L, Shorokhov R V, Yakushenko V K, Sokolov A V, Sennikov S V
Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russian Federation.
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russian Federation.
Scand J Immunol. 2015 Aug;82(2):110-7. doi: 10.1111/sji.12311.
Significant effort has been devoted to developing effective cancer vaccines based on dendritic cells (DCs) loaded with various tumour antigens, including DNA constructs that carry sequences of tumour-associated antigens (TAAs). Such vaccines efficiently and selectively activate the T cell immune response. In this study, we describe a method to induce an antitumour immune response in mononuclear cell (MNC) cultures from colorectal cancer patients using DNA-transfected DCs encoding TAA epitopes of carcinoembryonic antigen, epithelial cell adhesion molecule and mucin 4. DCs were obtained from peripheral blood monocytes of colorectal cancer patients. Magnetic-assisted transfection was used to deliver the genetic constructs to DCs. To assess the potency of the immune response, the antitumour cytotoxic response was assessed by lymphocyte intracellular perforin and the MNC cytotoxic activity against autologous tumour cells. We showed that polyepitope DNA-transfected DCs enhanced MNC antitumour activity, increasing tumour cell death and the percentage of perforin-positive lymphocytes. In addition, DNA-transfected DCs elicited a cytotoxic response that was as efficient as that of tumour lysate-loaded DCs. Taken together, the data suggest that it is feasible to induce an antitumour immune response in colorectal MNCs using transfected DCs. Thus, the DNA construct reported in this study may potentially be used in therapeutic and prophylactic DC-based vaccines.
人们付出了巨大努力来研发基于负载各种肿瘤抗原的树突状细胞（DCs）的有效癌症疫苗，这些抗原包括携带肿瘤相关抗原（TAAs）序列的DNA构建体。此类疫苗能有效且选择性地激活T细胞免疫反应。在本研究中，我们描述了一种利用编码癌胚抗原、上皮细胞粘附分子和粘蛋白4的TAA表位的DNA转染DCs，在结直肠癌患者的单核细胞（MNC）培养物中诱导抗肿瘤免疫反应的方法。DCs从结直肠癌患者的外周血单核细胞中获得。采用磁辅助转染将基因构建体递送至DCs。为评估免疫反应的效力，通过淋巴细胞内穿孔素和MNC对自体肿瘤细胞的细胞毒性活性来评估抗肿瘤细胞毒性反应。我们发现多表位DNA转染的DCs增强了MNC的抗肿瘤活性，增加了肿瘤细胞死亡以及穿孔素阳性淋巴细胞的百分比。此外，DNA转染的DCs引发的细胞毒性反应与负载肿瘤裂解物的DCs一样有效。综上所述，数据表明利用转染的DCs在结直肠癌MNCs中诱导抗肿瘤免疫反应是可行的。因此，本研究中报道的DNA构建体可能潜在地用于基于DCs的治疗性和预防性疫苗。
