Harnessing Cellular Immunotherapy for EBV-Associated Malignancies: Current Advances and Future Directions

Standard treatments for EBV-associated malignancies, such as chemotherapy and radiotherapy, demonstrate limited efficacy in relapsed or refractory cases, underscoring an urgent need for innovative therapeutic strategies. Recent advances in immunotherapy—particularly EBV-specific cytotoxic T lymphocytes and dendritic cell vaccines—have shown promise for both treatment and prevention. Engineered T cell therapies, including T-cell receptor (TCR) and chimeric antigen receptor (CAR) approaches targeting EBV antigens such as LMP1 and gp350, are progressing in clinical development. Compared to conventional intensive therapies, which often require prolonged administration and are associated with significant toxicity, cellular immunotherapy offers a favourable safety profile alongside robust in vivo T cell expansion and potent antitumor effects. Although preclinical and clinical trial results are encouraging, further refinement of therapeutic protocols is critical to enhance efficacy and improve access for diverse patient populations. In this review, we summarise the rationale for EBV-directed cellular therapies, outline their clinical applications to date, and discuss current limitations as well as emerging opportunities to optimise these strategies.