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CD87 靶向 BiTE 和 CAR-T 细胞能有效抑制侵袭性无功能垂体腺瘤。

CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

机构信息

Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

出版信息

Sci China Life Sci. 2024 Oct;67(10):2169-2185. doi: 10.1007/s11427-024-2591-7. Epub 2024 Jul 8.

Abstract

Recently, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor-modified T cells (CAR-Ts) have been shown to have high therapeutic efficacy in hematological tumors. CD87 is highly expressed in solid tumors with an oncogenic function. To assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas (iNFPAs), we first examined CD87 expression and its effects on the metabolism of iNFPA cells. We generated CD87-specific BiTE and CAR/IL-12 T cells, and their cytotoxic effects on iNFPAs cells and in mouse models were determined. CD87 had high expression in iNFPA tissue and cell samples but was undetected in noncancerous brain samples. CD87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects, decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental mice. Overall, the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

摘要

最近,双特异性 T 细胞衔接器(BiTEs)和嵌合抗原受体修饰的 T 细胞(CAR-Ts)已被证明在血液肿瘤中有很高的治疗效果。CD87 在具有致癌功能的实体瘤中高度表达。为了评估它们对侵袭性无功能垂体腺瘤(iNFPAs)的细胞毒性作用,我们首先检查了 CD87 的表达及其对 iNFPA 细胞代谢的影响。我们生成了 CD87 特异性 BiTE 和 CAR/IL-12 T 细胞,并确定了它们对 iNFPAs 细胞和小鼠模型的细胞毒性作用。CD87 在 iNFPAs 组织和细胞样本中高表达,但在非癌性脑组织样本中未检测到。CD87×CD3 BiTE 和 CD87 CAR/IL-12 T 细胞表现出抗原特异性,并发挥了令人满意的细胞毒性作用,体外减少了肿瘤细胞的增殖,并减少了实验小鼠的现有肿瘤。总的来说,上述发现表明,CD87 是使用抗 CD87 BiTE 和 CD87 特异性 CAR/IL-12 T 细胞对 iNFPAs 进行免疫治疗管理的有前途的靶标。

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