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

• Main Authors: Zhang Y, Duan X, Zhang W, Wu A, Yang H, Wu D, Wei Y, Chen X
• Format: Article
• Language: English
• Published: Dove Medical Press 2016-03-01
• Series: OncoTargets and Therapy
• Subjects: lung carcinoma; placenta-derived mesenchymal stem cells (pMSCs); attenuated vaccine; various irradiation levels
• Online Access: https://www.dovepress.com/antitumor-activity-of-pluripotent-cell-engineered-vaccines-and-their-p-peer-reviewed-article-OTT

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