Author:
Fan Shuangshuang,Wang Tian,You Fengtao,Zhang Tingting,Li Yafen,Ji Cheng,Han Zhichao,Sheng Binjie,Zhai Xiaochen,An Gangli,Meng Huimin,Yang Lin
Abstract
Abstract
Background and aims
Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in normal tissues is low. Therefore, B7-H3 is ideal for targeted AML therapy.
Materials and methods
First, we constructed B7-H3 CAR that can target B7-H3, and then constructed B7-H3-CAR-T cells in vitro, which were co-incubated with six AML cell lines expressing different levels of B7-H3, respectively. The toxicity and cytokines were detected by flow cytometry. In vivo, AML model was established in B-NSG mice to study the toxicity of B7-H3-CAR T on AML cells.
Results
In vitro functional tests showed that B7-H3-CAR-T cells were cytotoxic to B7-H3-positive AML tumor cells and had good scavenging effect on B7-H3-expressing AML cell lines, and the cytokine results were consistent. In vivo, B7-H3-CAR-T cells significantly inhibited tumor cell growth in a mouse model of AML, prolonging mouse survival compared with controls.
Conclusion
B7-H3-CAR-T cells may serve as a novel therapeutic method for the targeted treatment of AML.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Priority Academic Program Development of Jiangsu Higher Education Institutions, the Collaborative Innovation Major Project
Priority Academic Program Development of Jiangsu Higher Education Institutions, the Six Talent Peaks Project in Jiangsu Province
Natural Science Foundation of the Jiangsu Higher Education Institutions of China
Publisher
Springer Science and Business Media LLC
Cited by
5 articles.
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