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.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
抗体识别人表皮生长因子受体-2（HER2）近膜结构域增强嵌合抗原受体（CAR）-T 细胞的抗肿瘤应答
英文原题：Antibody Recognition of Human Epidermal Growth Factor Receptor-2 (HER2) Juxtamembrane Domain Enhances Anti-Tumor Response of Chimeric Antigen Receptor (CAR)-T Cells.
查看英文原题
Antibody Recognition of Human Epidermal Growth Factor Receptor-2 (HER2) Juxtamembrane Domain Enhances Anti-Tumor Response of Chimeric Antigen Receptor (CAR)-T Cells.
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中文摘要
CAR-T 细胞治疗恶性肿瘤前景良好，但靶向人表皮生长因子受体2（HER2）的CAR-T 可能因识别正常组织中的HER2而产生严重毒性，包括细胞因子释放综合征。改善HER2 CAR的质量和功能可能增强治疗潜力。本研究开发了新型抗HER2单克隆抗体Ab8，其识别HER2结构域III，与曲妥珠单抗识别的结构域IV不同。两种抗体诱导的抗体依赖性细胞毒作用相似，但基于曲妥珠单抗的CAR-T 对HER2阳性癌细胞显示强抗肿瘤活性。结果为抗体识别靠近细胞膜的结构域可促进HER2特异性CAR-T 抗肿瘤反应提供了证据。
展开英文摘要原文
Chimeric antigen receptor (CAR) T cell therapy shows promise in treating malignant tumors.
However, the use of human epidermal growth factor receptor-2 (HER2) CAR-T cells carries the risk of severe toxicity, including cytokine release syndrome, due to their "on-target off-tumor" recognition of HER2. Enhancing the quality and functionality of HER2 CARs could greatly improve the therapeutic potential of CAR-T cells.
In this study, we developed a novel anti-HER2 monoclonal antibody, Ab8, which targets domain III of HER2, distinct from the domain IV recognition of trastuzumab. Although two anti-HER2 mAbs induced similar levels of antibody-dependent cellular cytotoxicity, trastuzumab-based CAR-T cells exhibited potent antitumor activity against HER2-positive cancer cells.
In conclusion, our findings provide scientific evidence that antibody recognition of the membrane-proximal domain promotes the anti-tumor response of HER2-specific CAR-T cells.
论文信息
- 作者
- Zhou G、Fu S、Zhang Y、Li S、Guo Z、Ouyang D、Ying T、Lu Y
- 单位
- Institute of Translational Medicine, Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa 999078, Macau SAR, China.China
- 期刊
- Antibodies (Basel, Switzerland)2024 Jun 7
- 原文标识
- PubMed 38920969 · DOI 10.3390/antib13020045
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