Dendritic cells transfected with a polyepitope DNA construct stimulate an antitumor cytotoxic response in various tumors

用多表位DNA构建体转染的树突状细胞可刺激多种肿瘤产生抗肿瘤细胞毒性反应。

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作者:Vasily Kurilin ,Ekaterina Kulikova ,Julia Shevchenko ,Julia Lopatnikova ,Irina Obleukhova ,Julia Khantakova ,Amir Maksyutov ,Maria Kuznetsova ,Alexander Khristin ,Natalya Kiryshina ,Vadim Kozlov ,Sergey Sidorov ,Andrey Sokolov ,Alexander Vitsin ,Hiroshi Shiku ,Sergey Sennikov

Abstract

Dendritic cells (DCs) loaded with tumor-associated antigens (TAAs) are known to be crucial for the antitumor response and are still included in various treatment regimens in cancer immunotherapy research. In the present study, a cell-based protocol was evaluated, involving the use of original DNA constructs encoding the wide range of TAA epitopes expressed on different epithelial cancers. The constructs were transfected into in vitro-generated DCs of patients with various types of cancer, including breast, colorectal and non-small cell lung cancer. The direct cytotoxicity assay of effector cells, activated with the transfected DCs, revealed a significant increase in cytotoxicity against autologous tumor cells. The use of DNA constructs encoding a large number of TAAs for insertion into DCs in vitro, aiming to activate a T-cell response may prove to be a reliable and unified approach for immunotherapy and for the prevention of relapse in patients with epithelial cancers.

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