دورية أكاديمية
IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin
| العنوان: | IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin |
|---|---|
| المؤلفون: | Nengzhi Pang, Jingxuan Shi, Le Qin, Aiming Chen, Yuou Tang, Hainan Yang, Yufeng Huang, Qingde Wu, Xufeng Li, Bingjia He, Tianheng Li, Baoxia Liang, Jinglin Zhang, Bihui Cao, Manting Liu, Yunfei Feng, Xiaodie Ye, Xiaopei Chen, Lu Wang, Yu Tian, Hao Li, Junping Li, Hong Hu, Jingping He, Yuling Hu, Cheng Zhi, Zhaoyang Tang, Yibo Gong, Fangting Xu, Linfeng Xu, Weijun Fan, Ming Zhao, Deji Chen, Hui Lian, Lili Yang, Peng Li, Zhenfeng Zhang |
| المصدر: | Journal of Hematology & Oncology, Vol 14, Iss 1, Pp 1-6 (2021) |
| بيانات النشر: | BMC, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Diseases of the blood and blood-forming organs LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | CAR-T cell, IL-7, CCL19, Glypican-3, Mesothelin, Pancreatic carcinoma, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Abstract Although chimeric antigen receptor (CAR)-engineered T cells have shown great success in the treatment of B cell malignancies, this strategy has limited efficacy in patients with solid tumors. In mouse CAR-T cells, IL-7 and CCL19 expression have been demonstrated to improve T cell infiltration and CAR-T cell survival in mouse tumors. Therefore, in the current study, we engineered human CAR-T cells to secrete human IL-7 and CCL19 (7 × 19) and found that these 7 × 19 CAR-T cells showed enhanced capacities of expansion and migration in vitro. Furthermore, 7 × 19 CAR-T cells showed superior tumor suppression ability compared to conventional CAR-T cells in xenografts of hepatocellular carcinoma (HCC) cell lines, primary HCC tissue samples and pancreatic carcinoma (PC) cell lines. We then initiated a phase 1 clinical trial in advanced HCC/PC/ovarian carcinoma (OC) patients with glypican-3 (GPC3) or mesothelin (MSLN) expression. In a patient with advanced HCC, anti-GPC3-7 × 19 CAR-T treatment resulted in complete tumor disappearance 30 days post intratumor injection. In a patient with advanced PC, anti-MSLN-7 × 19 CAR-T treatment resulted in almost complete tumor disappearance 240 days post-intravenous infusion. Our results demonstrated that the incorporation of 7 × 19 into CAR-T cells significantly enhanced the antitumor activity against human solid tumor. Trial registration: NCT03198546. Registered 26 June 2017, https://clinicaltrials.gov/ct2/show/NCT03198546?term=NCT03198546&draw=2&rank=1 |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1756-8722 |
| Relation: | https://doaj.org/toc/1756-8722 |
| DOI: | 10.1186/s13045-021-01128-9 |
| URL الوصول: | https://doaj.org/article/679e8eb3ffae4847962f70d6239aac52 |
| رقم الأكسشن: | edsdoj.679e8eb3ffae4847962f70d6239aac52 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 17568722 |
|---|---|
| DOI: | 10.1186/s13045-021-01128-9 |