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

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 li...

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Autores principales: Lu, Jui-Hua, Peng, Bou-Yue, Chang, Chun-Chao, Dubey, Navneet Kumar, Lo, Wen-Cheng, Cheng, Hsin-Chung, Wang, Joseph R., Wei, Hong-Jian, Deng, Win-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266266/
https://www.ncbi.nlm.nih.gov/pubmed/30445793
http://dx.doi.org/10.3390/cancers10110446
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author Lu, Jui-Hua
Peng, Bou-Yue
Chang, Chun-Chao
Dubey, Navneet Kumar
Lo, Wen-Cheng
Cheng, Hsin-Chung
Wang, Joseph R.
Wei, Hong-Jian
Deng, Win-Ping
author_facet Lu, Jui-Hua
Peng, Bou-Yue
Chang, Chun-Chao
Dubey, Navneet Kumar
Lo, Wen-Cheng
Cheng, Hsin-Chung
Wang, Joseph R.
Wei, Hong-Jian
Deng, Win-Ping
author_sort Lu, Jui-Hua
collection PubMed
description 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.
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spelling pubmed-62662662018-12-03 Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine Lu, Jui-Hua Peng, Bou-Yue Chang, Chun-Chao Dubey, Navneet Kumar Lo, Wen-Cheng Cheng, Hsin-Chung Wang, Joseph R. Wei, Hong-Jian Deng, Win-Ping Cancers (Basel) Article 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. MDPI 2018-11-15 /pmc/articles/PMC6266266/ /pubmed/30445793 http://dx.doi.org/10.3390/cancers10110446 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lu, Jui-Hua
Peng, Bou-Yue
Chang, Chun-Chao
Dubey, Navneet Kumar
Lo, Wen-Cheng
Cheng, Hsin-Chung
Wang, Joseph R.
Wei, Hong-Jian
Deng, Win-Ping
Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
title Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
title_full Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
title_fullStr Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
title_full_unstemmed Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
title_short Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine
title_sort tumor-targeted immunotherapy by using primary adipose-derived stem cells and an antigen-specific protein vaccine
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266266/
https://www.ncbi.nlm.nih.gov/pubmed/30445793
http://dx.doi.org/10.3390/cancers10110446
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