Anti-mesothelin chimeric antigen receptor modified T cells for ovarian cancer
- Journal of Third Military Medical University Vol. 40, Issue 11, Pages: 945-953(2018)
- 作者机构：
- 作者简介：
- 基金信息：the General Program of National Natural Science Foundation of China(81572880);the Clinical Major New Technology Project of First Affiliated Hospital of Third Military Medical University(SWH2016ZDCX1005)
DOI：10.16016/j.1000-5404.201802124
CLC：Received：23 February 2018，
Published：2018-06
- 稿件说明：
移动端阅览
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.
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
2
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
2
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
2
Compared with normal tissues
ovarian cancer tissues highly expressed MSLN (
P
<
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
:1
the killing rate still remained at 80%. Moreover
the orthotopic xenografts of ovarian cancers in NOD/SCID mice disappeared completely after totally 1×10
7
MSLN-CART cells were injected
via
the tail vein twice.
Conclusion
2
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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