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
B7-H3 CAR-T 在肾细胞癌中疗效的临床前评估
英文原题：Preclinical assessment of the efficacy of B7-H3 CAR-T in renal cell carcinoma.
查看英文原题
Preclinical assessment of the efficacy of B7-H3 CAR-T in renal cell carcinoma.
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中文摘要
B7-H3是一种I型跨膜蛋白，属于B7免疫检查点蛋白家族，在癌细胞中异常表达而在正常组织中极少表达，因此是癌症治疗的一个有吸引力的靶点。我们发现B7-H3在肾细胞癌（RCC）肿瘤组织和RCC细胞系中高表达，而在正常肾组织中检测不到。因此，我们构建了靶向B7-H3的第二代CAR-T 细胞，分别采用CD28或4-1BB共刺激结构域。两种CAR-T 细胞均在体外以及转移性和原位RCC小鼠模型中对RCC肿瘤表现出强效抗肿瘤活性。此外，与RCC癌细胞共培养时，B7-H3 CAR-T 细胞显著增殖并大量释放细胞因子。这些发现表明，CAR-T 细胞靶向B7-H3可能为RCC患者提供一种新的治疗选择。
展开英文摘要原文
B7-H3 is a type I transmembrane protein that belongs to the B7 immune checkpoint protein family, is aberrantly expressed in cancer cells, but rarely expressed in normal tissues, making it an attractive target for cancer therapy.
Here, we found B7-H3 is highly expressed in the renal cell carcinoma (RCC) tumor tissues and RCC cell lines, but is undetectable in normal renal tissues.
Therefore, we engineered second-generation CAR-T cells targeting B7-H3, incorporating either CD28 or 4-1BB co-stimulatory domains. Both CAR-T cell variants demonstrated potent antitumor activity against RCC tumors in vitro and in metastatic and orthotopic RCC mouse models.
Furthermore, the B7-H3 CAR-T cells exhibited remarkable proliferation and robust cytokine release when co-cultured with RCC cancer cells.
These findings demonstrated that targeting B7-H3 by CAR-T cells potentially offering a new treatment option for RCC patients.
论文信息
- 作者
- Li H、Wang F、Zhao H、Cao J、Wang S、Li H、Savoldo B、Rao E
- 第一作者单位
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.China
- 通讯作者单位
- Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address: hwdu@xzhmu.edu.cn.China
- 文献类型
- 非美国政府资助研究 · 美国 NIH 资助研究
- 期刊
- Molecular immunology2024 Dec
- 原文标识
- PubMed 39514948 · DOI 10.1016/j.molimm.2024.10.006
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