Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape
We report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins—a low immunogenic variant of <i>Pseudomonas aeruginosa</i> exotoxin A and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/10/3014 |
| _version_ | 1797550645384839168 |
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| author | Elena Shramova Galina Proshkina Victoria Shipunova Anastasia Ryabova Roman Kamyshinsky Andrey Konevega Aleksey Schulga Elena Konovalova Georgij Telegin Sergey Deyev |
| author_facet | Elena Shramova Galina Proshkina Victoria Shipunova Anastasia Ryabova Roman Kamyshinsky Andrey Konevega Aleksey Schulga Elena Konovalova Georgij Telegin Sergey Deyev |
| author_sort | Elena Shramova |
| collection | DOAJ |
| description | We report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins—a low immunogenic variant of <i>Pseudomonas aeruginosa</i> exotoxin A and ribonuclease Barnase from <i>Bacillus amyloliquefaciens</i>. The delivery of toxins to cancer cells was carried out by targeting designed ankyrin repeat proteins (DARPins). We have shown that both target agents efficiently accumulate in the tumor. Simultaneous treatment of breast carcinoma-bearing mice with anti-EpCAM fusion toxin based on LoPE and HER2-specific liposomes loaded with Barnase leads to concurrent elimination of primary tumor and metastases. Monotherapy with anti-HER2- or anti-EpCAM-toxins did not produce a comparable effect on metastases. The proposed approach can be considered as a promising strategy for significant improvement of cancer therapy. |
| first_indexed | 2024-03-10T15:33:17Z |
| format | Article |
| id | doaj.art-352cc5239f1c45bd852ddd13d6c7f404 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T15:33:17Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-352cc5239f1c45bd852ddd13d6c7f4042023-11-20T17:26:50ZengMDPI AGCancers2072-66942020-10-011210301410.3390/cancers12103014Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor EscapeElena Shramova0Galina Proshkina1Victoria Shipunova2Anastasia Ryabova3Roman Kamyshinsky4Andrey Konevega5Aleksey Schulga6Elena Konovalova7Georgij Telegin8Sergey Deyev9Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaProkhorov General Physics Institute, Russian Academy of Sciences, Vavilova Street 38, 119991 Moscow, RussiaNational Research Center “Kurchatov Institute”, Akademika Kurchatova pl. 1, 123182 Moscow, RussiaNational Research Center “Kurchatov Institute”, Akademika Kurchatova pl. 1, 123182 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaShemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho–Maklaya Street 16/10, 117997 Moscow, RussiaWe report here a combined anti-cancer therapy directed toward HER2 and EpCAM, common tumor-associated antigens of breast cancer cells. The combined therapeutic effect is achieved owing to two highly toxic proteins—a low immunogenic variant of <i>Pseudomonas aeruginosa</i> exotoxin A and ribonuclease Barnase from <i>Bacillus amyloliquefaciens</i>. The delivery of toxins to cancer cells was carried out by targeting designed ankyrin repeat proteins (DARPins). We have shown that both target agents efficiently accumulate in the tumor. Simultaneous treatment of breast carcinoma-bearing mice with anti-EpCAM fusion toxin based on LoPE and HER2-specific liposomes loaded with Barnase leads to concurrent elimination of primary tumor and metastases. Monotherapy with anti-HER2- or anti-EpCAM-toxins did not produce a comparable effect on metastases. The proposed approach can be considered as a promising strategy for significant improvement of cancer therapy.https://www.mdpi.com/2072-6694/12/10/3014BarnaseliposomesHER2EpCAMcancer therapy |
| spellingShingle | Elena Shramova Galina Proshkina Victoria Shipunova Anastasia Ryabova Roman Kamyshinsky Andrey Konevega Aleksey Schulga Elena Konovalova Georgij Telegin Sergey Deyev Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape Cancers Barnase liposomes HER2 EpCAM cancer therapy |
| title | Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape |
| title_full | Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape |
| title_fullStr | Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape |
| title_full_unstemmed | Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape |
| title_short | Dual Targeting of Cancer Cells with DARPin-Based Toxins for Overcoming Tumor Escape |
| title_sort | dual targeting of cancer cells with darpin based toxins for overcoming tumor escape |
| topic | Barnase liposomes HER2 EpCAM cancer therapy |
| url | https://www.mdpi.com/2072-6694/12/10/3014 |
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