Rapid generation of genetically engineered T cells for the treatment of virus-related cancers

Jiang, Jinxing1,2; Xia, Ming1,2; Zhang, Lijie2,3; Chen, Xi4; Zhao, Yue4; Zeng, Chenquan1,2; Yang, Haiyan4; Liang, Peng4; Li, Guanghe2,5; Li, Ning1,2; Qi, Hui1,2; Wei, Teng1,2; Ren, Lili1,2

2022-09-01

10.1111/cas.15528

CANCER SCIENCE   Impact Factor & Quartile

1347-9032

1349-7006

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.

adoptive cell transfer HPV immunotherapy TCR-T cells virus-related cancers

SCI

English

Corresponding

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"]

Oncology

Oncology

WOS:000851444600001

WILEY

CLINICAL MEDICINE

Web of Science

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

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.

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.

Jiang, Jinxing,et al."Rapid generation of genetically engineered T cells for the treatment of virus-related cancers".CANCER SCIENCE (2022).