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The biological activity of bispecific trastuzumab/pertuzumab plant biosimilars may be drastically boosted by disulfiram increasing formaldehyde accumulation in cancer cellsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 декабря 2019 г.
- Авторы: Komarova Tatiana V., Sheshukova Ekaterina V., Kosobokova Ekaterina N., Kosorukov Vyacheslav S., Shindyapina Anastasia V., Lipskerov Fedor A., Shpudeiko Polina S., Byalik Tatiana E., Dorokhov Yuri L.
- Журнал: Scientific reports
- Том: 9
- Год издания: 2019
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 16168
- DOI: 10.1038/s41598-019-52507-9
- Аннотация: Studies of breast cancer therapy have examined the improvement of bispecific trastuzumab/pertuzumab antibodies interacting simultaneously with two different epitopes of the human epidermal growth factor receptor 2 (HER2). Here, we describe the creation and production of plant-made bispecific antibodies based on trastuzumab and pertuzumab plant biosimilars (bi-TPB-PPB). Using surface plasmon resonance analysis of bi-TPB-PPB antibodies binding with the HER2 extracellular domain, we showed that the obtained Kd values were within the limits accepted for modified trastuzumab and pertuzumab. Despite the ability of bi-TPB-PPB antibodies to bind to FcγRIIIa-receptor and HER2 oncoprotein on the cell surface, a proliferation inhibition assay did not reveal any effect until α1,3-fucose and β1,2-xylose in the Asn297-linked glycan were removed. Another approach to activating bi-TPB-PPB may be associated with the use of disulfiram (DSF) a known aldehyde dehydrogenase 2 (ALDH2) inhibitor. We found that disulfiram is capable of killing breast cancer cells with simultaneous formaldehyde accumulation. Furthermore, we investigated the capacity of DSF to act as an adjuvant for bi-TPB-PPB antibodies. Although the content of ALDH2 mRNA was decreased after BT-474 cell treatment with antibodies, we only observed cell proliferation inhibiting activity of bi-TPB-PPB in the presence of disulfiram. We concluded that disulfiram can serve as a booster and adjuvant for anticancer immunotherapy.
- Добавил в систему: Дорохов Юрий Леонидович
Прикрепленные файлы
| № | Имя | Описание | Имя файла | Размер | Добавлен |
|---|---|---|---|---|---|
| 1. | Komarova_19_SR.pdf | Komarova_19_SR.pdf | 2,4 МБ | 8 ноября 2019 [Dorokhov] | |
| 2. | 41598_2019_52507_Author_1.pdf | 41598_2019_52507_Author_1.pdf | 1,6 МБ | 30 октября 2019 [Dorokhov] | |
| 3. | Zimbra__Scientific_Reports__Decision_letter_for_SREP-19-263… | Zimbra__Scientific_Reports__Decision_letter_for_SREP-19-263… | 201,1 КБ | 19 октября 2019 [Dorokhov] |