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AAV‐mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune responseстатья
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: 23 декабря 2020 г.
- Авторы: Xia Yujia, He Jiayi, Zhang Hongji, Wang Han, Tetz George, Maguire Casey A., Wang Yu, Onuma Amblessed, Genkin Dmitry, Tetz Victor, Stepanov Alexey, Terekhov Stanislav, Ukrainskaya Valeria, Huang Hai, Tsung Allan
- Журнал: Molecular Oncology
- Том: 14
- Номер: 11
- Год издания: 2020
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 2920
- Последняя страница: 2935
- DOI: 10.1002/1878-0261.12787
- Аннотация: Liver metastasis is the main cause of colorectal cancer (CRC)‐related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long‐term daily administrations of recombinant DNase I, we have developed an adeno‐associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV‐mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV‐DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV‐DNase I and AAV‐null treatments. Our data suggest that AAV‐mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.
- Добавил в систему: Бачева Анна Владимировна