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通过嵌合抗原受体T细胞靶向B7H3治疗胃癌的抗肿瘤反应

Antitumor responses in gastric cancer by targeting B7H3 via chimeric antigen receptor T cells.

作者信息

Sun Fengqiang, Yu Xiaomei, Ju Ruixue, Wang Zhanzhao, Wang Yuhui

机构信息

Department of Clinical Laboratory, Weifang People's Hospital, Weifang, 261000, Shandong, China.

Department of Obstetrics, Weifang People's Hospital, Weifang, 261000, Shandong, China.

出版信息

Cancer Cell Int. 2022 Jan 31;22(1):50. doi: 10.1186/s12935-022-02471-8.

DOI:10.1186/s12935-022-02471-8
PMID:35101032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8802437/
Abstract

BACKGROUND

Gastric cancer (GC) has a poor prognosis and limited therapeutic options. As a new promising cancer therapeutic approach, chimeric antigen receptor (CAR)-T cells represent a potential GC treatment. We investigated the antitumor activity of CAR-T cells target-B7H3 in GC.

METHODS

In our study, expression of B7H3 was examined in GC tissues and explored the tumoricidal potential of B7H3-targeting CAR-T cells in GC. B7H3-directed CAR-T cells with a humanized antigen-recognizing domain was generated. The anti-tumor effects of this CAR-T cell were finally investigated in vitro and in vivo.

RESULTS

Our results show that B7H3-directed CAR-T cells efficiently killed GC tumor cells. In addition, we found that B7H3 is correlated with tumor cell stemness, and anti-B7H3 CAR-T can simultaneously target stem cell-like GC cells to improve the treatment outcome.

CONCLUSIONS

Our study indicates that B7H3 is an attractive target for GC therapy, and B7H3 has high potential for clinical application.

摘要

背景

胃癌(GC)预后较差且治疗选择有限。嵌合抗原受体(CAR)-T细胞作为一种新的有前景的癌症治疗方法,代表了一种潜在的胃癌治疗手段。我们研究了靶向B7H3的CAR-T细胞在胃癌中的抗肿瘤活性。

方法

在我们的研究中,检测了胃癌组织中B7H3的表达,并探讨了靶向B7H3的CAR-T细胞在胃癌中的杀瘤潜力。构建了具有人源化抗原识别结构域的靶向B7H3的CAR-T细胞。最终在体外和体内研究了这种CAR-T细胞的抗肿瘤作用。

结果

我们的结果表明,靶向B7H3的CAR-T细胞能有效杀伤胃癌肿瘤细胞。此外,我们发现B7H3与肿瘤细胞干性相关,抗B7H3 CAR-T可同时靶向干细胞样胃癌细胞以改善治疗效果。

结论

我们的研究表明,B7H3是胃癌治疗的一个有吸引力的靶点,且B7H3具有很高的临床应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b6a/8802437/089608ee8ef2/12935_2022_2471_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b6a/8802437/34bfdb23f17e/12935_2022_2471_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b6a/8802437/089608ee8ef2/12935_2022_2471_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b6a/8802437/a4e43f008039/12935_2022_2471_Fig5_HTML.jpg
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