| Autor: |
Lei Zhao, Yang Liu, Fuya Zhao, Ye Jin, Jing Feng, Rui Geng, Jiayu Sun, Liqing Kang, Lei Yu, Yunwei Wei |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Molecular Therapy: Oncolytics, Vol 16, Iss , Pp 262-271 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2372-7705 |
| DOI: |
10.1016/j.omto.2020.01.008 |
| Popis: |
This study aimed to assess the effectiveness of inhibiting cholesterol acyltransferase 1 (ACAT-1) in chimeric antigen receptor T (CAR-T) cells on potentiating the antitumor response against mesothelin (MSLN)-expressing pancreatic carcinoma (PC) cells. We engineered ACAT-1-inhibited CAR-T cells (CAR-T-1847 and CAR-T-1848) using the targeting MSLN CAR lentiviral vector and small interfering RNA (siRNA) targeting the conserved region of the ACAT-1 gene, and characterized the efficacy of these modified CAR-T cells in terms of the cytotoxicity and cytokine release of both MSLN-positive and MSLN-negative PC cells using in vitro methods and in vivo mouse xenografts. The ACAT-1-inhibited CAR-T-1847 and CAR-T-1848 cells showed a higher cytotoxicity at effector-to-target cell (E:T) ratios of 8:1 and 10:1, respectively, and induced a higher secretion of proinflammatory cytokines interleukin-2 (IL-2) and interferon-gamma (IFNγ) in vitro. In addition, bioluminescence imaging of tumor xenografts of ACAT-1-inhibited targeting MSLN CAR-T cells in MSLN-positive PC mice in vivo showed significant tumor regression, which is consistent with the in vitro observations. Our findings demonstrate a novel immunotherapeutic strategy involving the transplantation of ACAT-1-inhibited targeting MSLN CAR-T cells and the feasibility of enhancing the antitumor potency of CAR-T through the novel strategy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
