The Development of a Novel Cancer Immunotherapeutic Platform Using Tumor-targeting Mesenchymal Stem Cells and a Protein Vaccine |
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| Authors: | Hon-Jian Wei Alexander TH Wu Chung-Huei Hsu Yi-Ping Lin Wen-Fang Cheng Ching-Hua Su Wen-Ta Chiu Jacqueline Whang-Peng Frank L Douglas Win-Ping Deng |
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| Affiliation: | 1. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;2. Department of Radiation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;3. Translational Research Laboratory, Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan;4. Center of Excellence for Cancer Research, Taipei Medical University, Taipei, Taiwan;5. Department of Nuclear Medicine, Taipei Medical University Hospital, Taipei, Taiwan;6. Graduate Institute of Biomedical Materials and Engineering, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan;7. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan;8. College of Medicine, Taipei Medical University, Taipei, Taiwan;9. Division of Cancer Center, Wan Fang Hospital, Taipei, Taiwan;10. Austen BioInnovation Institute in Akron, Akron, Ohio, USA |
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| Abstract: | An ideal anticancer strategy should target only the malignant cells but spare the normal ones. In this regard, we established a platform, consisting of an antigen-delivering vehicle and a protein vaccine, for developing an immunotherapeutic approach with the potential for eliminating various cancer types. Mesenchymal stem cells (MSCs) have been demonstrated capable of targeting tumors and integrating into the stroma. Moreover, we have developed a protein vaccine PE(ΔIII)-E7-KDEL3 which specifically recognized E7 antigen and elicited immunity against cervical cancer. Taking advantage of tumor-homing property of MSCs and PE(ΔIII)-E7-KDEL3, we used E6/E7-immortalized human MSCs (KP-hMSCs) as an E7 antigen-delivering vehicle to test if this protein vaccine could effectively eliminate non-E7-expressing tumor cells. Animals which received combined treatment of KP-hMSCs and PE(ΔIII)-E7-KDEL3 demonstrated a significant inhibition of tumor growth and lung-metastasis when compared to PE(ΔIII)-E7-KDEL3 only and KP-hMSCs only groups. The efficiency of tumor suppression correlated positively to the specific immune response induced by PE(ΔIII)-E7-KDEL3. In addition, this combined treatment inhibited tumor growth via inducing apoptosis. Our findings indicated that KP-hMSCs could be used as a tumor-targeting device and mediate antitumor effect of PE(ΔIII)-E7-KDEL3. We believe this strategy could serve as a platform for developing a universal vaccine for different cancer types. |
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