Engineered T-Cells Show Promise in Targeting Epstein-Barr Virus-Associated Malignancies

Strategic Insights -

Investigators at Peking University Cancer Hospital and Institute have made a significant breakthrough in the development of engineered T-cells to target Epstein-Barr virus (EBV)-associated malignancies. According to a new report, the researchers have successfully identified and isolated Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T-cell receptors, which can be used to recognize and eliminate EBV-infected cells. 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.

Key Takeaways:

  • Researchers at Peking University Cancer Hospital and Institute have identified and isolated Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T-cell receptors.
  • The engineered T-cells demonstrated specific recognition of EBNA1 presented by autologous lymphoblastoid cell lines (LCLs) and dendritic cells (DCs) in vitro.
  • The study concludes that adoptive cell therapy targeting all EBV-associated malignancies, including latency I, is feasible using EBNA1-specific TCR-T cells.
  • The researchers used 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 to stimulate T cells.
  • 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.

Statistics:

  • EBNA1-specific T cells were successfully expanded from 1% to 50% after stimulation with autologous DCs pulsed with EBNA1 peptides.
  • Candidate EBNA1-specific TCRs with significantly increased frequencies were identified using high-throughput single-cell TCR V(D) J sequencing.
  • The research study was conducted at Peking University Cancer Hospital and Institute in Beijing, China.
  • The study was published in the journal Cellular Immunology (Volume 415-416, Issue 105002).
  • The research was supported by the Key Laboratory of Carcinogenesis and Translational Research Ministry of Education in China.

Sources:

  • [Research paper: Identification of Epstein-Barr virus nuclear antigen 1 (EBNA1)-specific T-cell receptors: implications for immunotherapy targeting EBV-associated malignancies. Cellular Immunology, 2025;415-416:105002]
  • [Journal contact information: Academic Press Inc Elsevier Science, 525 B St, Ste 1900, San Diego, CA 92101-4495, USA]
  • [Researcher contact information: Yaqi Pan, Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Beijing), Dept. of Genetics, Peking University Cancer Hospital and Institute, Beijing 100142, People's Republic of China]