title: Antitumor activity of pluripotent cell-engineered vaccines and their potential to treat lung cancer in relation to different levels of irradiation.
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.
authors.affiliation: 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.
authors.forename: Yan-Na
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Dong-Ming
authors.initials: DM
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Xian-Cheng
authors.initials: XC
authors.lastname: Chen
keywords: attenuated vaccine; irradiation level; lung carcinoma; placenta-derived mesenchymal stem cells (pMSCs)