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Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation

Authors Zhang Y, Duan X, Zhang W, Wu A, Yang H, Wu D, Wei Y, Chen X

Received 3 October 2015

Accepted for publication 12 January 2016

Published 11 March 2016 Volume 2016:9 Pages 1425—1436

DOI https://doi.org/10.2147/OTT.S97587

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Dekuang Zhao

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Yan-na Zhang, Xiao-gang Duan, Wen-hui Zhang, Ai-ling Wu, Huan-Huan Yang, Dong-ming Wu, Yu-Quan Wei, Xian-cheng Chen

State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China

Abstract: Cancer stem cells (CSCs) are critical for tumor initiation/maintenance and recurrence or metastasis, so they may serve as a potential therapeutic target. However, CSC-established multitherapy resistance and immune tolerance render tumors resistant to current tumor-targeted strategies. To address this, renewable multiepitope-integrated spheroids based on placenta-derived mesenchymal stem cells (pMSCs) were X-ray-modified, at four different irradiation levels, including 80, 160, 240, and 320 Gy, as pluripotent biologics, to inoculate hosts bearing Lewis lung carcinoma (LL2) and compared with X-ray-modified common LL2 cells as control. We show that the vaccines at the 160/240 Gy irradiation levels could rapidly trigger tumor cells into the apoptosis loop and evidently prolong the tumor-bearing host’s survival cycle, in contrast to vaccines irradiated at other levels (P<0.05), with tumor-sustaining stromal cell-derived factor-1/CXCR4 pathway being selectively blockaded. Meanwhile, almost no or minimal toxicity was detected in the vaccinated hosts. Importantly, 160/240 Gy-irradiated vaccines could provoke significantly higher killing of CSCs and non-CSCs, which may provide an access to developing a novel biotherapy against lung carcinoma.

Keywords: lung carcinoma, placenta-derived mesenchymal stem cells (pMSCs), attenuated vaccine, irradiation level

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