Switchable CAR-T Cells Outperformed Traditional AntibodyRedirected Therapeutics Targeting Breast Cancers

被引：24

作者：

Cao, Yu J. ^{[1
]}

Wang, Xuechun ^{[1
]}

Wang, Zhidong ^{[1
]}

Zhao, Lijun ^{[1
]}

Li, Shuhong ^{[1
]}

Zhang, Zhuxia ^{[1
]}

Wei, Xiaoyi ^{[1
]}

Yun, Hwayoung ^{[2
]}

Choi, Sei-Hyun ^{[3
]}

Liu, Zhong ^{[4
]}

Zhao, Lili ^{[5
]}

Kazane, Stephanie A. ^{[6
]}

机构：

[1] Peking Univ Shenzhen Grad Sch, State Key Lab Chem Oncogen, Key Lab Chem Genom, Shenzhen 518055, Guangdong, Peoples R China

[2] Pusan Natl Univ, Coll Pharm, Busan 46241, South Korea

[3] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[4] Shandong New Time Pharmaceut Co Ltd, Feixian Cty 273400, Shandong, Peoples R China

[5] State Engn Lab High Express Mammalian Cells, Feixian Cty 273400, Shandong, Peoples R China

[6] Calif Inst Biomed Res, La Jolla, CA 92037 USA

来源：

ACS SYNTHETIC BIOLOGY | 2021年 / 10卷 / 05期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

switchable CAR-T; CAR-T; bispecific antibodies; antibody-drug conjugates; unnatural amino acids; THERAPY; ACTIVATION; HER2;

D O I：

10.1021/acssynbio.1c00007

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Various antibody-redirected immunotherapeutic approaches, including antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs), and chimeric antigen receptor-T (CAR-T) cells, have been devised to produce specific activity against various cancer types. Using genetically encoded unnatural amino acids, we generated a homogeneous Her2-targeted ADC, a T cellredirected bsAb, and a FITC-modified antibody capable of redirecting anti-FITC CAR-T (switchable CAR-T; sCAR-T) cells to target different Her2-expressing breast cancers. sCAR-T cells showed activity against Her2-expressing tumor cells comparable to that of conventional anti-Her2 CAR-T cells and superior to that of ADC- and bsAb-based approaches. To prevent antigen escape, we designed bispecific sCAR-T cells targeting both the Her2 receptor and IGF1R, which showed an overall improved activity against cancer cells with low Her2 expression. This study increases our understanding of various explored cancer therapeutics and underscores the efficient application of sCAR-T cells as a promising therapeutic option for breast cancer patients with low or heterogeneous antigen expression.

引用

页码：1176 / 1183

页数：8

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