Research progression on the first-line biological target therapy of advanced
DOI：10.3872/j.issn.1007-385x.2020.08.003
- VernacularTitle:CD7纳米抗体衍生的CAR-T细胞对CD7阳性急性髓系白血病细胞的杀伤活性
- Author:
FAN Shuangshuang
1
;
ZHANG Tingting
1
;
WANG Tian
2
;
SHENG Binjie
3
;
YOU Fengtao
1
;
CHEN Dan
1
;
ZHAI Xiaochen
1
;
AN Gangli
1
;
MENG Huimin
1
;
YANG Lin
4
Author Information
1. 1a. Cyrus Tang Hematology Center,
2. 1b. Collaborative Innovation Center of Hematology
3. 1c. State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, Jiangsu, China
4. 2. Persongen BioTherapeutics (Suzhou) Co., Ltd, Suzhou 215123, Jiangsu, China)
- Publication Type:Journal Article
- Keywords:
chimeric antigen receptor gene modified-T lymphocytes (CAR-T);
CD7;
acute myeloid leukemia (AML);
apoptosis
- From:
Chinese Journal of Cancer Biotherapy
2020;27(8):852-859
- CountryChina
- Language:Chinese
-
Abstract:
[Abstract] Objective: To develop a new type of CD7 chimeric antigen receptor modified T cell (CD7-CAR-T) for the treatment of CD7 positive acute myeloid leukemia (AML), and to observe its killing effect on CD7 positive AML cells. Methods: The CD7-CAR lentiviral vector was constructed based on the CD7 Nanobody sequence and costimulatory domain sequence of CD28 and 4-1BB. The lentiviral particles were packaged and used to co-transfect human T cells with protein expression blocker (PEBL), so as to prepare CD7-
CAR-T cells. Real time cellular analysis (RTCA) was used to monitor the cytotoxicity of CD7-CAR-T cells on CD7 overexpressed 293T cells. Flow cytometry assay was used to detect the effect of CD7-CAR-T cells on proliferation and cytokine secretion of AML cells with high, medium and low CD7 expressions (KG-1, HEL and Kasumi-1 cells, respectively). Results: CD7-CAR-T cell was successfully constructed and its surface expression of CD7 was successfully blocked. Compared with T cells, CD7-CAR-T cells could significantly inhibit the proliferation of CD7-293T cells and promote the release of TNF, Granzyme B and INF-γ; in addition, CD7-CAR-T cells also significantly promoted the apoptosis (t=147.1, P<0.01; t=23.57, P<0.01) and cytokine release (P<0.05 or P<0.01) in CD7 positive KG-1 and HEL cells, but had little effect on Kasumi-1 cells that only expressed minimal CD7 antigen (t=0.7058, P>0.05). Conclusion: CD7-CAR-T cells can specifically kill CD7-positive AML cells in vitro.
- Full text:20200803.pdf
