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
靶向 B7-H3 的 CAR-T 细胞在结直肠癌患者来源类器官与肝异种移植模型中的显著细胞毒性作用
英文原题：The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients.
查看英文原题
The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients.
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研究概要
这些发现凸显了 B7-H3 CAR-T 细胞治疗转移性 CRC 的潜在疗效，并彰显了其转化价值。
研究思路结论见上方概要
背景
嵌合抗原受体（CAR）-T细胞在实体瘤中的应用因缺乏特异性肿瘤抗原和临床疗效有限而受到阻碍。我们的目标是开发并验证针对转移性结直肠癌（CRC）的新型CAR-T 细胞疗法。
方法
通过分别使用免疫组化（IHC）和流式细胞术分析B7-H3在CRC组织和细胞系中的表达，我们确定B7-H3为CRC中的一个潜在靶点。因此，我们开发了靶向B7-H3的CAR-T 细胞（B7-H3 CAR-T），并在体外和体内评估了其抗肿瘤活性，使用患者来源的类器官（PDOs）和异种移植（PDX）模型来验证其转化潜力。
结果
在我们170例CRC患者的队列中，通过IHC染色确定，与癌旁组织相比，B7-H3在CRC肿瘤中显著上调。当与CRC细胞或PDOs共培养时，B7-H3 CAR-T 细胞在体外表现出剂量依赖性细胞毒性。此外，B7-H3 CAR-T 细胞在体内有效控制肿瘤生长和转移，通过细胞毒性杀伤和潜在的免疫调节作用，显著延长了荷瘤小鼠的生存时间，这在基于CRC细胞和基于PDX的转移模型中均得到证实。
展开英文摘要原文
BACKGROUND
The application of chimeric antigen receptor (CAR)-T cells in solid tumors is hindered due to the lack of specific tumor antigen and limited clinical efficacy. Our aim is to develop and validate novel CAR-T cell therapy against metastatic colorectal cancer (CRC).
METHODS
By analyzing the expression of B7-H3 in CRC tissue and cell lines using immunohistochemistry (IHC) and flow cytometry, respectively, we identified B7-H3 as a potential target in CRC. We thereby developed CAR-T cells targeting B7-H3 (B7-H3 CAR-T) and evaluated their anti-tumor activity in vitro and in vivo, using patient-derived organoids (PDOs) and xenograft (PDX) models to validate its translational potential.
RESULTS
In our cohort of 170 CRC patients, B7-H3 was significantly upregulated in CRC tumors compared to paratumor tissue, as determined by IHC staining. When co-cultured with CRC cells or PDOs, B7-H3 CAR-T cells exhibited a dose-dependent cytotoxicity in vitro. Furthermore, B7-H3 CAR-T cells effectively controlled tumor growth and metastasis in vivo, significantly prolonging survival time for the tumor-burden mice through cytotoxic killing and potential immune regulatory effects, demonstrated in both CRC cell-based and PDX-based metastatic models.
CONCLUSIONS
These findings underscore the potential efficacy of B7-H3 CAR-T cells for treating metastatic CRC and highlight its translational value.
论文信息
- 作者
- Sheng Y、Yan L、Liu Q、Peng Y、Tan J、Li W、Mao W、Wei W
- 第一作者单位
- Key University Laboratory of Metabolism and Health of Guangdong, Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.China
- 通讯作者单位
- Cancer Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, PR China. dzza04606@btch.edu.cn.China
- 期刊
- British journal of cancer2025 Oct
- 原文标识
- PubMed 40721524 · DOI 10.1038/s41416-025-03114-1
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