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叶酸受体α靶向的 7x19 CAR-γδT 抑制小鼠三阴性乳腺癌异种移植模型

英文原题:Folate Receptor-Alpha Targeted 7x19 CAR-γδT Suppressed Triple-Negative Breast Cancer Xenograft Model in Mice.

查看英文原题

Folate Receptor-Alpha Targeted 7x19 CAR-γδT Suppressed Triple-Negative Breast Cancer Xenograft Model in Mice.

PubMed 2022/03/07(内容时间) J Oncol

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研究概要

我们的结果表明,7 × 19 CAR-γδ T 具有显著的抗 TNBC 肿瘤活性,在治疗无法治愈的 TNBC 患者中显示出广阔的应用前景。

研究思路结论见上方概要

三阴性乳腺癌(TNBC)是预后最差的乳腺癌亚型,因为缺乏特异性靶点。近期研究表明,免疫治疗可能通过靶向叶酸受体α(FRα)来解决这一问题。

基因修饰的γδ T细胞被制备为表达FRa特异性嵌合抗原受体(FRa CAR)并分泌白细胞介素-7(IL-7)和趋化因子C-C基序配体19(CCL19)。分泌IL-7和CCL19的CAR-γδ T细胞(7 × 19 CAR-γδ T)在体外和体内均被评估了其抗肿瘤活性。

7 × 19 CAR-γδ T在体外显示出显著的抗肿瘤活性。与PBMC联合使用时,7 × 19 CAR-γδ T对TNBC异种移植模型生长的抑制作用优于单用或常规CAR-γδ T细胞。组织病理学分析显示DC或T细胞向肿瘤组织的浸润增加。

展开英文摘要原文

Triple-negative breast cancer (TNBC) is the worst prognosis subtype of breast cancer due to lack of specific targets. Recent studies have shown that immunotherapy may solve that problem by targeting folate receptor-alpha (FR α ).

Gene modified γδ T cells were manufactured to express FRa specific chimeric antigen receptor (FRa CAR) and secrete interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19). CAR- γδ T cells that secrete IL-7 and CCL19 (7 × 19 CAR- γδ T) were evaluated for their antitumor activity both in vitro and in vivo.

7 × 19 CAR- γδ T showed remarkable antitumor activity in vitro. Combined with PBMC, 7 × 19 CAR- γδ T inhibited TNBC xenograft model growth superiorly compared with single-application or conventional CAR- γδ T cells. Histopathological analyses showed increased DC or T cells infiltration to tumor tissues.

Taken together, our results showed that 7 × 19 CAR- γδ T have remarkable anti-TNBC tumor activity and showed a broad application prospect in the treatment of incurable TNBC patients.

论文信息

作者
Ye X、Deng X、Wen J、Li Y、Zhang M、Cai Z、Liu G、Wang H
单位
Department of Surgery, Hebei Medical University, Shijiazhuang 050051, Hebei Province, China.China
期刊
Journal of oncology2022
原文标识
PubMed 35295709 · DOI 10.1155/2022/2112898