Title | Rapid generation of genetically engineered T cells for the treatment of virus-related cancers |
Author | |
Corresponding Author | Wei, Teng; Ren, Lili |
Publication Years | 2022-09-01
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DOI | |
Source Title | |
ISSN | 1347-9032
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EISSN | 1349-7006
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Abstract | Adoptive transfer of T cell receptor (TCR)-engineered T cells targeting viral epitopes represents a promising approach for treating virus-related cancers. However, the efficient identification of epitopes for T cells and the corresponding TCR remains challenging. Here, we report a workflow permitting the rapid generation of human papillomavirus (HPV)-specific TCR-T cells. Six epitopes of viral proteins belonged to HPV16 or HPV18 were predicted to have high affinity to A11:01 according to bioinformatic analysis. Subsequently, CTL induction were performed with these six antigen peptides separately, and antigen-specific T cells were sorted by FACS. TCR clonotypes of these virus-specific T cells were determined using next-generation sequencing. To improve the efficiency of TCR alpha beta pair validation, a lentiviral vector library containing 116 TCR constructs was generated that consisted of predominant TCRs according to TCR repertoire analysis. Later, TCR library transduced T cells were simulated with peptide pool-pulsed antigen-presenting cells, then CD137-positive cells were sorted and subjected to TCR repertoire analysis. The top-hit TCRs and corresponding antigen peptides were deduced and validated. Through this workflow, a TCR targeting the E6(92-101) of HPV16 was identified. These HPV16-specific TCR-T cells showed high activity towards HPV16-positive human cervical cancer cells in vitro and efficiently repressed tumor growth in a murine model. This study provides a HPV16-specific TCR fitted to the HLA-A11:01 population, and exemplifies an efficient approach that can be applied in large-scale screening of virus-specific TCRs, further encouraging researchers to exploit the therapeutic potential of the TCR-T cell technique in treating virus-related cancers. |
Keywords | |
URL | [Source Record] |
Indexed By | |
Language | English
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SUSTech Authorship | Corresponding
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Funding Project | Guangdong Basic and Applied Basic Research Foundation[2019A1515110149]
; National Natural Science Foundation of China[82002956]
; Shenzhen International Collaborative Innovation Program["GJHZ20190821162003794","GJHZ20210705142209028"]
; Shenzhen Natural Science Foundation["JCYJ20190807150615224","JCYJ20210324114009026"]
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WOS Research Area | Oncology
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WOS Subject | Oncology
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WOS Accession No | WOS:000851444600001
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Publisher | |
ESI Research Field | CLINICAL MEDICINE
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Data Source | Web of Science
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Citation statistics |
Cited Times [WOS]:0
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Document Type | Journal Article |
Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/401522 |
Department | Shenzhen People's Hospital |
Affiliation | 1.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Cytotherapy Lab, Shenzhen, Guangdong, Peoples R China 2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Guangdong, Peoples R China 3.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Gynecol, Shenzhen, Guangdong, Peoples R China 4.RootPath Inc, Watertown, MA USA 5.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Pharm, Shenzhen, Guangdong, Peoples R China |
First Author Affilication | Shenzhen People's Hospital |
Corresponding Author Affilication | Shenzhen People's Hospital |
Recommended Citation GB/T 7714 |
Jiang, Jinxing,Xia, Ming,Zhang, Lijie,et al. Rapid generation of genetically engineered T cells for the treatment of virus-related cancers[J]. CANCER SCIENCE,2022.
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APA |
Jiang, Jinxing.,Xia, Ming.,Zhang, Lijie.,Chen, Xi.,Zhao, Yue.,...&Ren, Lili.(2022).Rapid generation of genetically engineered T cells for the treatment of virus-related cancers.CANCER SCIENCE.
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MLA |
Jiang, Jinxing,et al."Rapid generation of genetically engineered T cells for the treatment of virus-related cancers".CANCER SCIENCE (2022).
|
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