| Autor: |
Tong Li, Jiandong Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
BMC Cancer, Vol 20, Iss 1, Pp 1-13 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1471-2407 |
| DOI: |
10.1186/s12885-020-07180-x |
| Popis: |
Abstract Background More favorable treatment against epithelial ovarian cancer (EOC) is urgently needed because of its insidious nature at an early stage and a low rate of five-year survival. The current primary treatment, extensive surgery combined with chemotherapy, exhibits limited benefits for improving prognosis. Chimeric antigen receptor T (CAR-T) cell technology as novel immunotherapy has made breakthrough progress in the treatment of hematologic malignancies, and there were also benefits shown in a partial solid tumor in previous research. Therefore, CAR-T cell technology may be a promising candidate as an immunotherapeutic tool against EOC. However, there are some weaknesses in targeting one antigen from the previous preclinical assay, such as on-target off-tumor cytotoxicity. The dual-target CAR-T cell may be a better choice. Methods We constructed tandem PD1-antiMUC16 dual-CAR, PD1 single-CAR, and anti-MUC16 single-CAR fragments by PCR and genetic engineering, followed by preparing CAR-T cells via lentiviral infection. The expression of CAR molecules on single and dual CAR-T cells was detected by flow cytometry. The killing capacity and activation of CAR-T cells were measured by cytotoxic assays and cytokines release assays in vitro. The therapeutic capacity of CAR-T cells was assessed by tumor-bearing mice model assay in vivo. Results We successfully constructed CARs lentiviral expression vectors and obtained single and dual CAR-T cells. CAR-T cells demonstrated robust killing capacity against OVCAR-3 cells in vitro. Meanwhile, CAR-T cells released plenty of cytokines such as interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α(TNF-α). CAR-T cells showed a therapeutic benefit against OVCAR-3 tumor-bearing mice and significantly prolonged the survival time. Dual CAR-T cells were shown to be two to four times more efficacious than single CAR-T cells in terms of survival time. Conclusion Although exhibiting a similar ability as single CAR-T cells against OVCAR-3 cells in vitro, dual CAR-T cells demonstrated enhanced killing capacity against OVCAR-3 cells as compared to single CAR-T cells in vivo and significantly prolonged the survival time of tumor-bearing mice. PD1-antiMUC16 CAR-T cells showed more potent antitumor activity than single CAR-T cells in vivo. The present experimental data may support further research work that will have the potential to lead to clinical studies. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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