Engineering In Vitro Organ-Structured Tumor Model for Evaluating Neoantigen-Specific T Cell Responses in Hepatocellular Carcinoma

Xiao, Jingyu1; Wang, Fei2,3,4; Hu, Xiaoyan5; Li, Dongli6; Liu, Geng6; Xu, Qumiao3; Chen, Chao7; Xiang, Haitao3; Dong, Xuan3; Zhu, Linnan8; Yang, Dishuang1,3; Gao, Yanan1; Wang, Meijuan1; Luo, Yonglun2,3,4; Chao, Cheng-Chi9; Li, Guanglei10; Guo, Qiongyu1

2023-07-01

10.1002/admi.202300155

ADVANCED MATERIALS INTERFACES   影响因子和分区

2196-7350

Neoantigens derived from somatic mutations in cancer cells can induce antigen-specific T-cell immune response for cancer immunotherapy. However, the 3D models for assessing neoepitope immunogenicity and efficacy of anti-tumor T-cell immune response to neoantigens are less than perfect. Here, a 3D tumor model based on recellularized liver matrix is leveraged with HepG2 cells to investigate T cell cytotoxic reactivity toward hepatocellular carcinoma (HCC) neoantigens. The whole exome sequencing (WES) data of 364 HCC patients in The Cancer Genome Atlas database are collected and 25 highly potential immunogenic neoantigens to human leukocyte antigen (HLA)-A*02:01 molecule in silico are predicted. Six of the HCC neoantigen candidates are functionally validated with high immunogenicity by measuring cellular interferon-& gamma; secretion and cytotoxicity during neoantigen-specific T-cell immune responses in vitro. Then, the minigene of six functionally identified neoantigen peptides is constructed and the minigene-modified GFP-HepG2 cells are generated. Neoantigen-specific immune response is observed with highly secreted Granzyme B, IFN-& gamma;, and PD-1 when targeting the minigene-modified GFP-HepG2 cells in the 3D RLM HCC tumor model. Overall, the 3D RLM tumor model provides a novel strategy for preclinical assessment of the efficacy of neoantigen-specific T cell immune response, which helps develop personalized cancer vaccines and immunotherapy treatments for HCC patients.

cancer immunotherapy hepatocellular carcinoma minigene modified HepG2 cells neoantigens recellularized liver matrix

SCI ; EI

英语

第一 ; 通讯

National Natural Science Foundation of China[81971764] ; Guangdong Research Fund[2019ZT08Y191] ; Key-Area Research and Development Program of Guangdong Province[2019B010941001] ; Innovation Committee of Shenzhen Municipality[JCYJ20200109141638004] ; Guangdong Provincial Key Laboratory of Advanced Biomaterials[2022B1212010003] ; Shenzhen Key Laboratory of Smart Healthcare Engineering[ZDSYS20200811144003009] ; Special Fund for Science Technology Innovation and Industrial Development of Shenzhen Dapeng New District[CXY202001-02]

Chemistry ; Materials Science

Chemistry, Multidisciplinary ; Materials Science, Multidisciplinary

WOS:001032027200001

WILEY

20233014426295

3D modeling ; Antigens ; Cancer cells ; Cell engineering ; Cytology ; Diseases ; Immune system ; Tumors ; Vaccines

Biomedical Engineering:461.1 ; Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Biology:461.9 ; Immunology:461.9.1 ; Data Processing and Image Processing:723.2

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen Key Lab Smart Healthcare Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen 518055, Guangdong, Peoples R China
2.Aarhus Univ, Dept Biomed, DK-8000 Aarhus, Denmark
3.BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China
4.Qingdao Europe Adv Inst Life Sci, Lars Bolund Inst Regenerat Med, BGI Qingdao, Qingdao 266555, Shandong, Peoples R China
5.Chinese Acad Sci, Inst Biomed & Biotechnol, Shenzhen Inst Adv Technol, Shenzhen Key Lab Biomimet Mat & Cellular Immunomod, Shenzhen 518055, Guangdong, Peoples R China
6.GenoImmune Shenzhen, Shenzhen 518083, Guangdong, Peoples R China
7.Hong Kong Univ Sci & Technol, Peking Univ Shenzhen Hosp, Shenzhen Peking Univ, Med Ctr,Dept Thorac Surg, Shenzhen 518035, Peoples R China
8.Peking Univ, BIOPIC, Beijing 100871, Peoples R China
9.Biomap Inc, Dept Pipeline Dev, San Francisco, CA 94025 USA
10.Cheerland Co Shenzhen, Shenzhen 518083, Guangdong, Peoples R China

Xiao, Jingyu,Wang, Fei,Hu, Xiaoyan,et al. Engineering In Vitro Organ-Structured Tumor Model for Evaluating Neoantigen-Specific T Cell Responses in Hepatocellular Carcinoma[J]. ADVANCED MATERIALS INTERFACES,2023,10.

Xiao, Jingyu.,Wang, Fei.,Hu, Xiaoyan.,Li, Dongli.,Liu, Geng.,...&Guo, Qiongyu.(2023).Engineering In Vitro Organ-Structured Tumor Model for Evaluating Neoantigen-Specific T Cell Responses in Hepatocellular Carcinoma.ADVANCED MATERIALS INTERFACES,10.

Xiao, Jingyu,et al."Engineering In Vitro Organ-Structured Tumor Model for Evaluating Neoantigen-Specific T Cell Responses in Hepatocellular Carcinoma".ADVANCED MATERIALS INTERFACES 10(2023).