T Cells Expressing CAR Equipped With Extracellular Domain of BTLA Are Effective Against HVEM-over-expressing Melanoma Cell Lines

被引：1

作者：

Kim, Yeongrin ^{[1
,2
]}

Kim, Ji Eun ^{[1
]}

Lee, Da Yeon ^{[1
,3
]}

Choi, Ji U. ^{[1
,2
]}

Park, Jin Song ^{[1
]}

Lee, Heung Kyoung ^{[1
]}

Choi, Sang Un ^{[1
]}

Park, Simon ^{[4
]}

Park, Chi Hoon ^{[1
,2
]}

机构：

[1] Korea Res Inst Chem Technol, Bio & Drug Discovery Div, 141 Gajeong Ro, Daejeon 34114, South Korea

[2] Korea Univ Sci & Technol, Med Chem & Pharmacol, Daejeon, South Korea

[3] Chungnam Natl Univ, Coll Pharm, Daejeon, South Korea

[4] Abtironbio, Hanam Si, South Korea

来源：

ANTICANCER RESEARCH | 2023年 / 43卷 / 08期

关键词：

CAR T cell therapy; melanoma; solid tumor; HVEM; BTLA; immunology; THERAPY; PROGRESSION; CANCER;

D O I：

10.21873/anticanres.16517

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: Several chimeric antigen receptor (CAR) T cells have been used to treat melanoma but have not shown favorable results. This study investigated whether Herpes virus entry mediator (HVEM), which is over -expressed in melanoma, is a potential novel antigen for CAR T cell therapy. Materials and Methods: A CAR construct, composed of the BTLA extracellular domain for HVEM recognition (BTLA-28z), was developed and tested. Results: Jurkat cells transduced with BTLA-28z exhibited enhanced IL -2 secretion when incubated with HVEM-over-expressing melanoma cells. KHYG-1 cells transduced with BTLA-28z also lysed melanoma cell lines. Using primary T cells, we generated CAR T cells targeting HVEM. BTLA-28z CAR T cells exhibited excellent lytic activities against melanoma cell lines. Conclusion: HVEM-targeting CAR T cells may be useful for the treatment of melanoma.

引用

页码：3419 / 3427

页数：9

共 28 条

[1] A High Molecular Weight Melanoma-Associated Antigen-Specific Chimeric Antigen Receptor Redirects Lymphocytes to Target Human Melanomas [J].

Burns, William R. ;

Zhao, Yangbing ;

Frankel, Timothy L. ;

Hinrichs, Christian S. ;

Zheng, Zhili ;

Xu, Hui ;

Feldman, Steven A. ;

Ferrone, Soldano ;

Rosenberg, Steven A. ;

Morgan, Richard A. .

CANCER RESEARCH, 2010, 70 (08) :3027-3033

[2] Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial [J].

Dai, Hanren ;

Tong, Chuan ;

Shi, Daiwei ;

Chen, Meixia ;

Guo, Yelei ;

Chen, Deyun ;

Han, Xiao ;

Wang, Hua ;

Wang, Yao ;

Shen, Pingping .

ONCOIMMUNOLOGY, 2020, 9 (01)

[3] Tonic 4-1BB Costimulation in Chimeric Antigen Receptors Impedes T Cell Survival and Is Vector-Dependent [J].

Gomes-Silva, Diogo ;

Mukherjee, Malini ;

Srinivasan, Madhuwanti ;

Krenciute, Giedre ;

Dakhova, Olga ;

Zheng, Yueting ;

Cabral, Joaquim M. S. ;

Rooney, Cliona M. ;

Orange, Jordan S. ;

Brenner, Malcolm K. ;

Mamonkin, Maksim .

CELL REPORTS, 2017, 21 (01) :17-26

[4] Immune checkpoint molecule herpes virus entry mediator is overexpressed and associated with poor prognosis in human glioblastoma [J].

Han, Ming-Zhi ;

Wang, Shuai ;

Zhao, Wen-Bo ;

Ni, Shi-Lei ;

Yang, Ning ;

Kong, Yang ;

Huang, Bin ;

Chen, An-Jing ;

Li, Xin-Gang ;

Wang, Jian ;

Wang, Dong-Hai .

EBIOMEDICINE, 2019, 43 :159-170

[5] Genetically modified CD7-targeting allogeneic CAR-T cell therapy with enhanced efficacy for relapsed/refractory CD7-positive hematological malignancies: a phase I clinical study [J].

Hu, Yongxian ;

Zhou, Yali ;

Zhang, Mingming ;

Zhao, Houli ;

Wei, Guoqing ;

Ge, Wengang ;

Cui, Qu ;

Mu, Qitian ;

Chen, Gong ;

Han, Lu ;

Guo, Tingting ;

Cui, Jiazhen ;

Jiang, Xiaoyan ;

Zheng, Xiujun ;

Yu, Shuhui ;

Li, Xiaolong ;

Zhang, Xingwang ;

Chen, Mingxi ;

Li, Xiuju ;

Gao, Ming ;

Wang, Kang ;

Zu, Cheng ;

Zhang, Hao ;

He, Xiaohong ;

Wang, Yanbin ;

Wang, Dongrui ;

Ren, Jiangtao ;

Huang, He .

CELL RESEARCH, 2022, 32 (11) :995-1007

[6]

Inoue T, 2015, ANTICANCER RES, V35, P1361

[7] Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma [J].

Krishnamurthy, Janani ;

Rabinovich, Brian A. ;

Mi, Tiejuan ;

Switzer, Kirsten C. ;

Olivares, Simon ;

Maiti, Sourindra N. ;

Plummer, Joshua B. ;

Singh, Harjeet ;

Kumaresan, Pappanaicken R. ;

Huls, Helen M. ;

Wang-Johanning, Feng ;

Cooper, Laurence J. N. .

CLINICAL CANCER RESEARCH, 2015, 21 (14) :3241-3251

[8] Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis [J].

Lan, Xiuwen ;

Li, Sen ;

Gao, Hongyu ;

Nanding, Abiyasi ;

Quan, Lina ;

Yang, Chunyan ;

Ding, Shaohua ;

Xue, Yingwei .

ONCOTARGETS AND THERAPY, 2017, 10 :919-926

[9] Sequential different B-cell antigen-targeted CAR T-cell therapy for pediatric refractory/relapsed Burkitt lymphoma [J].

Liu, Ying ;

Deng, Biping ;

Hu, Bo ;

Zhang, Wenqun ;

Zhu, Qing ;

Liu, Yang ;

Wang, Shan ;

Zhang, Pei ;

Yang, Ying ;

Yang, Junhan ;

Zheng, Qinlong ;

Yu, Xinjian ;

Gao, Zifen ;

Zhou, Chunju ;

Han, Wei ;

Yang, Jing ;

Jin, Ling ;

Tong, Chunrong ;

Chang, Alex H. ;

Zhang, Yonghong .

BLOOD ADVANCES, 2022, 6 (03) :717-730

[10] Current Progress in CAR-T Cell Therapy for Solid Tumors [J].

Ma, Shuo ;

Li, Xinchun ;

Wang, Xinyue ;

Cheng, Liang ;

Li, Zhong ;

Zhang, Changzheng ;

Ye, Zhenlong ;

Qian, Qijun .

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2019, 15 (12) :2548-2560

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