CD87靶向BiTE和CAR-T细胞能有效抑制侵袭性无功能垂体腺瘤。

IF 8 2区 生物学 Q1 BIOLOGY Science China Life Sciences Pub Date : 2024-10-01 Epub Date: 2024-07-08 DOI:10.1007/s11427-024-2591-7
Yuan Ren, Xinjie Bao, Ming Feng, Bing Xing, Wei Lian, Yong Yao, Renzhi Wang
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引用次数: 0

摘要

最近,双特异性 T 细胞诱导体(BiTEs)和嵌合抗原受体修饰 T 细胞(CAR-Ts)被证明对血液肿瘤有很高的疗效。CD87 在实体瘤中高度表达,具有致癌功能。为了评估它们对侵袭性无功能垂体腺瘤(iNFPA)的细胞毒性作用,我们首先研究了 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,并测定了它们对 iNFPAs 细胞和小鼠模型的细胞毒性作用。CD87 在 iNFPA 组织和细胞样本中高表达,但在非癌症脑样本中未检测到。CD87×CD3 BiTE 和 CD87 CAR/IL-12 T 细胞显示了抗原特异性,并发挥了令人满意的细胞毒性作用,在体外减少了肿瘤细胞的增殖,在实验小鼠体内减少了现有的肿瘤。总之,上述研究结果表明,CD87是利用抗CD87 BiTE和CD87特异性CAR/IL-12 T细胞对iNFPAs进行免疫治疗的一个很有前景的靶点。
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CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas.

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.

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来源期刊
CiteScore
15.10
自引率
8.80%
发文量
2907
审稿时长
3.2 months
期刊介绍: Science China Life Sciences is a scholarly journal co-sponsored by the Chinese Academy of Sciences and the National Natural Science Foundation of China, and it is published by Science China Press. The journal is dedicated to publishing high-quality, original research findings in both basic and applied life science research.
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