CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
CD24 是 CAR-T 细胞治疗三阴性乳腺癌的新靶点
英文原题：CD24 is a novel target of chimeric antigen receptor T cells for the treatment of triple negative breast cancer.
查看英文原题
CD24 is a novel target of chimeric antigen receptor T cells for the treatment of triple negative breast cancer.
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中文摘要
三阴性乳腺癌（TNBC）是恶性程度最高、预后最差的乳腺癌亚型。免疫治疗在TNBC中的应用有限。本研究旨在验证靶向CD24的CAR-T 细胞（CAR-T 细胞，命名为24BBz）在TNBC治疗中的潜在应用。通过慢病毒感染构建24BBz，然后与乳腺癌细胞系共培养，以评估工程化T细胞的活化、增殖和细胞毒性。在裸鼠皮下异种移植模型中验证了24BBz的抗肿瘤活性。我们发现CD24基因在乳腺癌（BRCA）中显著上调，尤其是在TNBC中。24BBz在体外对CD24阳性BRCA肿瘤细胞表现出抗原特异性活化和剂量依赖性细胞毒性。此外，24BBz在CD24阳性TNBC异种移植瘤中显示出显著的抗肿瘤效果，肿瘤组织中有T细胞浸润，同时部分T细胞表现出耗竭。治疗期间未发现主要器官的病理性损伤。本研究证明CD24特异性CAR-T 细胞具有强效抗肿瘤活性，在TNBC治疗中具有潜在应用价值。
展开英文摘要原文
Triple negative breast cancer (TNBC) is a subtype of breast cancer with the highest degree of malignancy and the worst prognosis. The application of immunotherapy for TNBC is limited.
This study was to verify the potential application of chimeric antigen receptor-T cells (CAR-T cells) targeting CD24 named as 24BBz in treatment of TNBC. 24BBz was constructed by lentivirus infection and then was co-culture with breast cancer cell lines to evaluate the activation, proliferation and cytotoxicity of engineered T cells. The anti-tumor activity of 24BBz was verified in the subcutaneous xenograft model of nude mice.
We found that CD24 gene was significantly up-regulated in breast cancer (BRCA), especially in TNBC. 24BBz showed antigen-specific activation and dose-dependent cytotoxicity against CD24-positive BRCA tumor cells in vitro.
Furthermore, 24BBz showed significant anti-tumor effect in CD24-positive TNBC xenografts and T cells infiltration in tumor tissues, while some T cells exhibited exhaustion. No pathological damage of major organs was found during the treatment.
This study proved that CD24-specific CAR-T cells have potent anti-tumor activity and potential application value in treatment of TNBC.
论文信息
- 作者
- Yang P、Yu F、Yao Z、Ding X、Xu H、Zhang J
- 第一作者单位
- The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, People's Republic of China.China
- 通讯作者单位
- Antibody Engineering Laboratory, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. zhangjuan@cpu.edu.cn.China
- 期刊
- Cancer immunology, immunotherapy : CII2023 Oct
- 原文标识
- PubMed 37418008 · DOI 10.1007/s00262-023-03491-7
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