|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ИНХС РАН |
||
Genetically Modified DR5-Specific TRAIL Variant DR5-B Revealed Dual Antitumor and Protumoral Effect in Colon Cancer Xenografts and an Improved Pharmacokinetic Profileстатья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 19 августа 2020 г.
- Авторы: Yagolovich Anne V., Artykov Artem A., Karmakova Tatiana A., Vorontsova Maria S., Pankratov Andrey A., Andreev-Andrievsky Alexander A., Dolgikh Dmitry A., Kirpichnikov Mikhail P., Gasparian Marine E.
- Журнал: Translational Oncology
- Том: 13
- Номер: 4
- Год издания: 2020
- Издательство: Neoplasia Press
- Местоположение издательства: United States
- Первая страница: 100762
- DOI: 10.1016/j.tranon.2020.100762
- Аннотация: Despite the weak clinical efficacy of TRAIL death receptor agonists, a search is under way for new agents that more efficiently activate apoptotic signaling. We previously created a TRAIL DR5-selective variant DR5-B without affinity for the DR4, DcR1, DcR2, and OPG receptors and increased proapoptotic activity in tumor cells. Here we showed that DR5-B significantly inhibited tumor growth in HCT116 and Caco-2 but not in HT-29 xenografts. The antitumor activity of DR5-B was 2.5 times higher in HCT116 xenografts compared to TRAIL. DR5-B at a dose of 2 or 10 mg/kg/d for 10 days inhibited tumor growth in HCT116 xenografts by 26% or 50% respectively, and increased animal survival. Unexpectedly, DR5-B at a higher dose (25 mg/kg/d) inhibited tumor growth only during the first 8 days of drug exposure, while at the end of the monitoring, no effect or even slight stimulation of tumor growth was observed. The pharmacokinetic parameters of DR5-B were comparable to those of TRAIL, except that the half-life was 3.5 times higher. Thus, enhancing TRAIL selectivity to DR5 may increase both antitumor and proliferative activities depending on the concentration and administration regimens.
- Добавил в систему: Андреев-Андриевский Александр Александрович