Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy
Oncolytic adenoviruses (Ads) are promising tools for cancer therapeutics. However, most Ad-based therapies utilize Ad type 5 (Ad5), which displays unsatisfying efficiency in clinical trials, partly due to the low expression levels of its primary coxsackievirus and adenovirus receptor (CAR) on tumor...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/6/1403 |
| _version_ | 1797566641095049216 |
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| author | Nicolas Mach Jian Gao Lukas Schaffarczyk Sebastian Janz Eric Ehrke-Schulz Thomas Dittmar Anja Ehrhardt Wenli Zhang |
| author_facet | Nicolas Mach Jian Gao Lukas Schaffarczyk Sebastian Janz Eric Ehrke-Schulz Thomas Dittmar Anja Ehrhardt Wenli Zhang |
| author_sort | Nicolas Mach |
| collection | DOAJ |
| description | Oncolytic adenoviruses (Ads) are promising tools for cancer therapeutics. However, most Ad-based therapies utilize Ad type 5 (Ad5), which displays unsatisfying efficiency in clinical trials, partly due to the low expression levels of its primary coxsackievirus and adenovirus receptor (CAR) on tumor cells. Since the efficacy of virotherapy strongly relies on efficient transduction of targeted tumor cells, initial screening of a broad range of viral agents to identify the most effective vehicles is essential. Using a novel Ad library consisting of numerous human Ads representing known Ad species, we evaluated the transduction efficiencies in four breast cancer (BC) cell lines. For each cell line over 20 Ad types were screened in a high-throughput manner based on reporter assays. Ad types featuring high transduction efficiencies were further investigated with respect to the percentage of transgene-positive cells and efficiencies of cellular entry in individual cell lines. Additionally, oncolytic assay was performed to test tumor cell lysis efficacy of selected Ad types. We found that all analyzed BC cell lines show low expression levels of CAR, while alternative receptors such as CD46, DSG-2, and integrins were also detected. We identified Ad3, Ad35, Ad37, and Ad52 as potential candidates for BC virotherapy. |
| first_indexed | 2024-03-10T19:29:18Z |
| format | Article |
| id | doaj.art-0b97802f79764c8c898bbd85a7bea99f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:29:18Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-0b97802f79764c8c898bbd85a7bea99f2023-11-20T02:12:11ZengMDPI AGCancers2072-66942020-05-01126140310.3390/cancers12061403Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer TherapyNicolas Mach0Jian Gao1Lukas Schaffarczyk2Sebastian Janz3Eric Ehrke-Schulz4Thomas Dittmar5Anja Ehrhardt6Wenli Zhang7Virology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyInstitute of Immunology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyVirology and Microbiology, Center for Biomedical Education and Research (ZBAF), Department of Human Medicine, Faculty of Health, Witten/Herdecke University, 58453 Witten, GermanyOncolytic adenoviruses (Ads) are promising tools for cancer therapeutics. However, most Ad-based therapies utilize Ad type 5 (Ad5), which displays unsatisfying efficiency in clinical trials, partly due to the low expression levels of its primary coxsackievirus and adenovirus receptor (CAR) on tumor cells. Since the efficacy of virotherapy strongly relies on efficient transduction of targeted tumor cells, initial screening of a broad range of viral agents to identify the most effective vehicles is essential. Using a novel Ad library consisting of numerous human Ads representing known Ad species, we evaluated the transduction efficiencies in four breast cancer (BC) cell lines. For each cell line over 20 Ad types were screened in a high-throughput manner based on reporter assays. Ad types featuring high transduction efficiencies were further investigated with respect to the percentage of transgene-positive cells and efficiencies of cellular entry in individual cell lines. Additionally, oncolytic assay was performed to test tumor cell lysis efficacy of selected Ad types. We found that all analyzed BC cell lines show low expression levels of CAR, while alternative receptors such as CD46, DSG-2, and integrins were also detected. We identified Ad3, Ad35, Ad37, and Ad52 as potential candidates for BC virotherapy.https://www.mdpi.com/2072-6694/12/6/1403adenovirusadenovirus receptorsbreast cancerbroad spectrumcellular entryhigh-throughput screening |
| spellingShingle | Nicolas Mach Jian Gao Lukas Schaffarczyk Sebastian Janz Eric Ehrke-Schulz Thomas Dittmar Anja Ehrhardt Wenli Zhang Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy Cancers adenovirus adenovirus receptors breast cancer broad spectrum cellular entry high-throughput screening |
| title | Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy |
| title_full | Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy |
| title_fullStr | Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy |
| title_full_unstemmed | Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy |
| title_short | Spectrum-Wide Exploration of Human Adenoviruses for Breast Cancer Therapy |
| title_sort | spectrum wide exploration of human adenoviruses for breast cancer therapy |
| topic | adenovirus adenovirus receptors breast cancer broad spectrum cellular entry high-throughput screening |
| url | https://www.mdpi.com/2072-6694/12/6/1403 |
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