Ying Liu , Yaqi Pan , Huirong Ding , Wei He , Huanyu Chen , Zhe Hu , Zheming Lu , Yang Ke
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For pre-stimulated and post-stimulated T cells, candidate EBNA1-specific TCRs with significantly increased frequencies were identified using high-throughput single-cell TCR V(D) J sequencing. The functionality of EBNA1-specific TCR-engineered T cells was assessed <em>in vitro</em> against lymphoblastoid cell lines (LCLs) and EBNA1 peptide-pulsed DCs.</div></div><div><h3>Results</h3><div>EBNA1-specific T cells were successfully expanded. Candidate EBNA1-specific TCRs were isolated, corresponding TCR gene sequences were constructed and introduced into peripheral blood T cells. Engineered T cells expressing EBNA1-specific TCR demonstrated specific recognition of EBNA1 presented by autologous LCLs and DCs <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>This study establishes the feasibility of expanding functional EBNA1-specific TCR-T cells, providing a foundation for adoptive cell therapy targeting all EBV-associated malignancies, including latency I.</div></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"415 ","pages":"Article 105002"},"PeriodicalIF":2.9000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T-cell receptors: implications for immunotherapy targeting EBV-associated malignancies\",\"authors\":\"Ying Liu , Yaqi Pan , Huirong Ding , Wei He , Huanyu Chen , Zhe Hu , Zheming Lu , Yang Ke\",\"doi\":\"10.1016/j.cellimm.2025.105002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Epstein-Barr virus nuclear antigen (EBNA1) is uniquely expressed across all three EBV latency types, making it an ideal target for TCR-engineered T-cell therapy against EBV-associated malignancies. However, preparation of EBNA1-specific TCR-T cells, particularly for EBV latency I type, remains exploratory.</div></div><div><h3>Methods</h3><div>EBNA1-specific T cells were stimulated using autologous dendritic cells (DCs) pulsed with peptides synthesized from the complete sequence (except the glycine-alanine repeat region) of the EBNA1 of EBV strain B95–8. For pre-stimulated and post-stimulated T cells, candidate EBNA1-specific TCRs with significantly increased frequencies were identified using high-throughput single-cell TCR V(D) J sequencing. The functionality of EBNA1-specific TCR-engineered T cells was assessed <em>in vitro</em> against lymphoblastoid cell lines (LCLs) and EBNA1 peptide-pulsed DCs.</div></div><div><h3>Results</h3><div>EBNA1-specific T cells were successfully expanded. Candidate EBNA1-specific TCRs were isolated, corresponding TCR gene sequences were constructed and introduced into peripheral blood T cells. Engineered T cells expressing EBNA1-specific TCR demonstrated specific recognition of EBNA1 presented by autologous LCLs and DCs <em>in vitro</em>.</div></div><div><h3>Conclusions</h3><div>This study establishes the feasibility of expanding functional EBNA1-specific TCR-T cells, providing a foundation for adoptive cell therapy targeting all EBV-associated malignancies, including latency I.</div></div>\",\"PeriodicalId\":9795,\"journal\":{\"name\":\"Cellular immunology\",\"volume\":\"415 \",\"pages\":\"Article 105002\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0008874925000887\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0008874925000887","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Identification of Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T-cell receptors: implications for immunotherapy targeting EBV-associated malignancies
Background
Epstein-Barr virus nuclear antigen (EBNA1) is uniquely expressed across all three EBV latency types, making it an ideal target for TCR-engineered T-cell therapy against EBV-associated malignancies. However, preparation of EBNA1-specific TCR-T cells, particularly for EBV latency I type, remains exploratory.
Methods
EBNA1-specific T cells were stimulated using autologous dendritic cells (DCs) pulsed with peptides synthesized from the complete sequence (except the glycine-alanine repeat region) of the EBNA1 of EBV strain B95–8. For pre-stimulated and post-stimulated T cells, candidate EBNA1-specific TCRs with significantly increased frequencies were identified using high-throughput single-cell TCR V(D) J sequencing. The functionality of EBNA1-specific TCR-engineered T cells was assessed in vitro against lymphoblastoid cell lines (LCLs) and EBNA1 peptide-pulsed DCs.
Results
EBNA1-specific T cells were successfully expanded. Candidate EBNA1-specific TCRs were isolated, corresponding TCR gene sequences were constructed and introduced into peripheral blood T cells. Engineered T cells expressing EBNA1-specific TCR demonstrated specific recognition of EBNA1 presented by autologous LCLs and DCs in vitro.
Conclusions
This study establishes the feasibility of expanding functional EBNA1-specific TCR-T cells, providing a foundation for adoptive cell therapy targeting all EBV-associated malignancies, including latency I.
期刊介绍:
Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered.
Research Areas include:
• Antigen receptor sites
• Autoimmunity
• Delayed-type hypersensitivity or cellular immunity
• Immunologic deficiency states and their reconstitution
• Immunologic surveillance and tumor immunity
• Immunomodulation
• Immunotherapy
• Lymphokines and cytokines
• Nonantibody immunity
• Parasite immunology
• Resistance to intracellular microbial and viral infection
• Thymus and lymphocyte immunobiology
• Transplantation immunology
• Tumor immunity.