抗间皮素嵌合抗原受体修饰T细胞治疗卵巢癌的实验研究

杨永君; 李瑶; 尹立; 刘新东; 卞修武; 余时沧

doi:10.16016/j.1000-5404.201802124

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抗间皮素嵌合抗原受体修饰T细胞治疗卵巢癌的实验研究

基础医学 | 更新时间：2026-01-09

- 抗间皮素嵌合抗原受体修饰T细胞治疗卵巢癌的实验研究
- Anti-mesothelin chimeric antigen receptor modified T cells for ovarian cancer
- 第三军医大学学报 2018年40卷第11期页码：945-953
- 作者机构：
- 作者简介：
- 基金信息：
  
  国家自然科学基金面上项目(81572880);第三军医大学第一附属医院重大领域技术创新项目(SWH2016ZDCX1005)
- DOI：10.16016/j.1000-5404.201802124
  中图分类号：
- 收稿：2018-02-23，
  
  纸质出版：2018-06
- 稿件说明：
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杨永君, 李瑶, 尹立, 等. 抗间皮素嵌合抗原受体修饰T细胞治疗卵巢癌的实验研究[J]. 第三军医大学学报, 2018,40(11):945-953.

Yongjun YANG, Yao LI, Li YIN, et al. Anti-mesothelin chimeric antigen receptor modified T cells for ovarian cancer[J]. Journal of Third Military Medical University, 2018, 40(11): 945-953.
杨永君, 李瑶, 尹立, 等. 抗间皮素嵌合抗原受体修饰T细胞治疗卵巢癌的实验研究[J]. 第三军医大学学报, 2018,40(11):945-953. DOI： 10.16016/j.1000-5404.201802124.

Yongjun YANG, Yao LI, Li YIN, et al. Anti-mesothelin chimeric antigen receptor modified T cells for ovarian cancer[J]. Journal of Third Military Medical University, 2018, 40(11): 945-953. DOI： 10.16016/j.1000-5404.201802124.

摘要

Abstract

Objective

To observe the killing effect of anti-mesothelin (MSLN) chimeric antigen receptor (CAR) modified T cells (CART) for ovarian cancer cells

and explore new treatment methods and strategies for the tumor.

Methods

A humanized CAR structure of anti-human MSLN was designed and ligated to a lentiviral vector. Human peripheral blood mononuclear cells were infected with associate lentivirus for introduction of CART. Western blotting

qRT-PCR and flow cytometry were used to detect the correct expression of CAR structure on the membrane surface of CART. The expression of MSLN in ovarian cancer samples and cell lines was

detected by immunohistochemical assay and Western blotting. The cytotoxicity of the CART cells to kill MSLN-positive ovarian cancer cells was evaluated

via

in vitro

and

in vivo

experiments.

Results

Compared with normal tissues

ovarian cancer tissues highly expressed MSLN (

0.01); The anti-MSLN-CART cells were successfully prepared

and these cells specifically recognized and killed MSLN-positive ovarian cancer cells

in vitro

experiments. When the E:T ratio was 2

-4

the killing rate still remained at 80%. Moreover

the orthotopic xenografts of ovarian cancers in NOD/SCID mice disappeared completely after totally 1×10

MSLN-CART cells were injected

via

the tail vein twice.

Conclusion

Anti-MSLN-CART cells can effectively

specifically and safely kill ovarian cancer cells

inhibit the growth of tumors.

关键词

Keywords

references

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