Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime
Lung cancer is one of the most commonly diagnosed cancer and despite therapeutic advances, mortality remains high. The long period of clinical latency associated with lung cancer provides an ideal window of opportunity to administer vaccines to at-risk individuals that can prevent tumor progression...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01996/full |
| _version_ | 1818278996948811776 |
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| author | Zhe Zhang Shuangshuang Lu Louisa S. Chard Dunmall Zhizhong Wang Zhenguo Cheng Zhongxian Zhang Wenli Yan Yongchao Chu Dongling Gao Na Wang Yang Li Jiwei Wang Yuenan Li Yupei Ji Danyang Shan Keke Li Panpan Wang Yunshu Dong Jianzeng Dong Nick R. Lemoine Nick R. Lemoine Duanqing Pei Lirong Zhang Yaohe Wang Yaohe Wang |
| author_facet | Zhe Zhang Shuangshuang Lu Louisa S. Chard Dunmall Zhizhong Wang Zhenguo Cheng Zhongxian Zhang Wenli Yan Yongchao Chu Dongling Gao Na Wang Yang Li Jiwei Wang Yuenan Li Yupei Ji Danyang Shan Keke Li Panpan Wang Yunshu Dong Jianzeng Dong Nick R. Lemoine Nick R. Lemoine Duanqing Pei Lirong Zhang Yaohe Wang Yaohe Wang |
| author_sort | Zhe Zhang |
| collection | DOAJ |
| description | Lung cancer is one of the most commonly diagnosed cancer and despite therapeutic advances, mortality remains high. The long period of clinical latency associated with lung cancer provides an ideal window of opportunity to administer vaccines to at-risk individuals that can prevent tumor progression and initiate long-term anti-tumor immune surveillance. Here we describe a personalized vaccination regime that could be applied for both therapeutic and prophylactic prevention of lung cancer, based on the derivation of lung cancer cells from induced pluripotent stem cells. Stem cells from healthy mice were modified to express Cre-dependent KRASG12D and Trp53R172H prior to differentiation to lung progenitor cells. Subsequent viral delivery of Cre caused activation of exogenous driver mutations, resulting in transformation and development of lung cancer cells. iPSC-derived lung cancer cells were highly antigenically related to lung cancer cells induced in LSL-KRASG12D/+; Trp53R172H/+ transgenic mice and were antigenically unrelated to original pluripotent stem cells or pancreatic cancer cells derived using the same technological platform. For vaccination, induced lung cancer cells were infected with oncolytic Adenovirus or Vaccinia virus, to act as vaccine adjuvants, prior to delivery of vaccines sequentially to a murine inducible transgenic model of lung cancer. Application of this Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime primed tumor-specific T cell responses that significantly prolonged survival in both subcutaneous post-vaccine challenge models and induced transgenic models of lung cancer, demonstrating that stem cell-derived prophylactic vaccines may be a feasible intervention for treatment or prevention of lung cancer development in at-risk individuals. |
| first_indexed | 2024-12-12T23:26:19Z |
| format | Article |
| id | doaj.art-0732dd0f70924129bc3cb791a7c0317e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T23:26:19Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-0732dd0f70924129bc3cb791a7c0317e2022-12-22T00:08:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-08-011110.3389/fimmu.2020.01996545029Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) RegimeZhe Zhang0Shuangshuang Lu1Louisa S. Chard Dunmall2Zhizhong Wang3Zhenguo Cheng4Zhongxian Zhang5Wenli Yan6Yongchao Chu7Dongling Gao8Na Wang9Yang Li10Jiwei Wang11Yuenan Li12Yupei Ji13Danyang Shan14Keke Li15Panpan Wang16Yunshu Dong17Jianzeng Dong18Nick R. Lemoine19Nick R. Lemoine20Duanqing Pei21Lirong Zhang22Yaohe Wang23Yaohe Wang24National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaCentre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United KingdomNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaCAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaDepartment of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaCentre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United KingdomCAS Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaSchool of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaNational Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaCentre for Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, United KingdomLung cancer is one of the most commonly diagnosed cancer and despite therapeutic advances, mortality remains high. The long period of clinical latency associated with lung cancer provides an ideal window of opportunity to administer vaccines to at-risk individuals that can prevent tumor progression and initiate long-term anti-tumor immune surveillance. Here we describe a personalized vaccination regime that could be applied for both therapeutic and prophylactic prevention of lung cancer, based on the derivation of lung cancer cells from induced pluripotent stem cells. Stem cells from healthy mice were modified to express Cre-dependent KRASG12D and Trp53R172H prior to differentiation to lung progenitor cells. Subsequent viral delivery of Cre caused activation of exogenous driver mutations, resulting in transformation and development of lung cancer cells. iPSC-derived lung cancer cells were highly antigenically related to lung cancer cells induced in LSL-KRASG12D/+; Trp53R172H/+ transgenic mice and were antigenically unrelated to original pluripotent stem cells or pancreatic cancer cells derived using the same technological platform. For vaccination, induced lung cancer cells were infected with oncolytic Adenovirus or Vaccinia virus, to act as vaccine adjuvants, prior to delivery of vaccines sequentially to a murine inducible transgenic model of lung cancer. Application of this Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime primed tumor-specific T cell responses that significantly prolonged survival in both subcutaneous post-vaccine challenge models and induced transgenic models of lung cancer, demonstrating that stem cell-derived prophylactic vaccines may be a feasible intervention for treatment or prevention of lung cancer development in at-risk individuals.https://www.frontiersin.org/article/10.3389/fimmu.2020.01996/fulllung cancervaccineinduced pluripotent stem cellsKRASTP53adenovirus |
| spellingShingle | Zhe Zhang Shuangshuang Lu Louisa S. Chard Dunmall Zhizhong Wang Zhenguo Cheng Zhongxian Zhang Wenli Yan Yongchao Chu Dongling Gao Na Wang Yang Li Jiwei Wang Yuenan Li Yupei Ji Danyang Shan Keke Li Panpan Wang Yunshu Dong Jianzeng Dong Nick R. Lemoine Nick R. Lemoine Duanqing Pei Lirong Zhang Yaohe Wang Yaohe Wang Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime Frontiers in Immunology lung cancer vaccine induced pluripotent stem cells KRAS TP53 adenovirus |
| title | Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime |
| title_full | Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime |
| title_fullStr | Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime |
| title_full_unstemmed | Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime |
| title_short | Treatment and Prevention of Lung Cancer Using a Virus-Infected Reprogrammed Somatic Cell-Derived Tumor Cell Vaccination (VIReST) Regime |
| title_sort | treatment and prevention of lung cancer using a virus infected reprogrammed somatic cell derived tumor cell vaccination virest regime |
| topic | lung cancer vaccine induced pluripotent stem cells KRAS TP53 adenovirus |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01996/full |
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