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

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

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 thi...

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Main Authors: Zhang, Yan-na, Duan, Xiao-gang, Zhang, Wen-hui, Wu, Ai-ling, Yang, Huan-Huan, Wu, Dong-ming, Wei, Yu-Quan, Chen, Xian-cheng
Format: Online
Language:English
Published: Dove Medical Press 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795574/
id pubmed-4795574
recordtype oai_dc
spelling pubmed-47955742016-04-01 Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation Zhang, Yan-na Duan, Xiao-gang Zhang, Wen-hui Wu, Ai-ling Yang, Huan-Huan Wu, Dong-ming Wei, Yu-Quan Chen, Xian-cheng Original Research 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. Dove Medical Press 2016-03-11 /pmc/articles/PMC4795574/ /pubmed/27042111 http://dx.doi.org/10.2147/OTT.S97587 Text en © 2016 Zhang et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Zhang, Yan-na
Duan, Xiao-gang
Zhang, Wen-hui
Wu, Ai-ling
Yang, Huan-Huan
Wu, Dong-ming
Wei, Yu-Quan
Chen, Xian-cheng
spellingShingle Zhang, Yan-na
Duan, Xiao-gang
Zhang, Wen-hui
Wu, Ai-ling
Yang, Huan-Huan
Wu, Dong-ming
Wei, Yu-Quan
Chen, Xian-cheng
Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
author_facet Zhang, Yan-na
Duan, Xiao-gang
Zhang, Wen-hui
Wu, Ai-ling
Yang, Huan-Huan
Wu, Dong-ming
Wei, Yu-Quan
Chen, Xian-cheng
author_sort Zhang, Yan-na
title Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
title_short Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
title_full Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
title_fullStr Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
title_full_unstemmed Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
title_sort antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation
description 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.
publisher Dove Medical Press
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795574/
_version_ 1613553050013663232

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