Antibody Recognition of Human Epidermal Growth Factor Receptor-2 (HER2) Juxtamembrane Domain Enhances Anti-Tumor Response of Chimeric Antigen Receptor (CAR)-T Cells

被引：3

作者：

Zhou, Guangyu ^{[1
,2
]}

Fu, Shengyu ^{[1
]}

Zhang, Yunsen ^{[3
]}

Li, Shuang ^{[4
]}

Guo, Ziang ^{[1
]}

Ouyang, Defang ^{[3
]}

Ying, Tianlei ^{[5
]}

Lu, Yinying ^{[4
]}

Zhao, Qi ^{[1
,2
]}

机构：

[1] Univ Macau, Inst Translat Med, Fac Hlth Sci, Canc Ctr, Taipa 999078, Macau, Peoples R China

[2] Univ Macau, MoE Frontiers Sci Ctr Precis Oncol, Taipa 999078, Macau, Peoples R China

[3] Univ Macau, Inst Chinese Med Sci, Taipa 999078, Macau, Peoples R China

[4] Peoples Liberat Army Gen Hosp, Med Ctr 5, Beijing 100036, Peoples R China

[5] Fudan Univ, Shanghai Inst Infect Dis & Biosecur, Shanghai Engn Res Ctr Synthet Immunol, MOE NHC CAMS Key Lab Med Mol Virol,Sch Basic Med S, Shanghai 200032, Peoples R China

来源：

ANTIBODIES | 2024年 / 13卷 / 02期

基金：

国家重点研发计划;

关键词：

HER2; monoclonal antibody; CAR-T cell; trastuzumab; BREAST-CANCER; T-CELLS; HERCEPTIN;

D O I：

10.3390/antib13020045

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：12

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