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Cancers (Basel). 2018 Nov 15;10(11). pii: E446. doi: 10.3390/cancers10110446.

Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine.

Lu JH1,2, Peng BY3,4, Chang CC5,6, Dubey NK7,8, Lo WC9,10, Cheng HC11, Wang JR12, Wei HJ13,14, Deng WP15,16,17.

Author information

1
Graduate Institute of Biomedical Materials and Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 110, Taiwan. d225101001@tmu.edu.tw.
2
Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. d225101001@tmu.edu.tw.
3
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. pemg@tmu.edu.tw.
4
Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan. pemg@tmu.edu.tw.
5
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110i, Taiwan. chunchao@tmu.edu.tw.
6
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University School of Medicine, Taipei 110, Taiwan. chunchao@tmu.edu.tw.
7
Ceramics and Biomaterials Research Group, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam. navneet.kumar.dubey@tdtu.edu.vn.
8
Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 700000, Vietnam. navneet.kumar.dubey@tdtu.edu.vn.
9
Department of Neurosurgery, Taipei Medical University Hospital, Taipei 110, Taiwan. d102092012@tmu.edu.tw.
10
School of Medicine, Taipei Medical University, Taipei 110, Taiwan. d102092012@tmu.edu.tw.
11
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. g4808@tmu.edu.tw.
12
Department of Periodontics, College of Dental Medicine, Columbia University, New York 10032, USA. jrw2166@cumc.columbia.edu.
13
Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. hjwei@tmu.edu.tw.
14
School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. hjwei@tmu.edu.tw.
15
Stem Cell Research Center, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. wpdeng@tmu.edu.tw.
16
School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. wpdeng@tmu.edu.tw.
17
Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City 110, Taiwan. wpdeng@tmu.edu.tw.

Abstract

Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7' antigen (E7') as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7' (ADSC-E7'-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer.

KEYWORDS:

T cell responses; adipose-derived stem cells; antigen processing; protein vaccine; tumor microenvironment

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