Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T

作者：Jiajia Wang, Huiping Wang, Yangyang Ding, Na Cao, Feng-Ya Nan, Fan Wu, Cong Li, Xue Liang, Meng Xiao, Jinjing Guo, Zhimai Gao, Yan Li, Tielin Zhou, Yanli Li, Zhimin Zhai · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06188-w · 被引用次数：8 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Monoclonal and Polyclonal Antibodies Research

BACKGROUND: Epstein-Barr virus (EBV) is an oncovirus belonging to the herpesvirus family, associated with the pathogenesis of multiple malignancies, particularly Burkitt lymphoma (BL). The virus remains latent in host cells and plays a critical role in tumor progression through various mechanisms. A key glycoprotein, gp350, expressed during the lytic phase of EBV, is instrumental in viral entry into B cells and presents a unique antigenic target, making it a promising candidate for immunotherapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) therapy. METHODS: In this study, we engineered CAR-T cells targeted against the gp350 glycoprotein and assessed their therapeutic potential through a series of in vitro and in vivo experiments. The efficacy of the gp350-CAR-T cells was evaluated by comparing their cytotoxic effects against both EBV-positive and -negative tumor cell lines. We utilized a xenograft model of Burkitt lymphoma to monitor the impact of gp350-CAR-T cell administration on tumor progression and overall survival. RESULTS: The engineered gp350-CAR-T cells demonstrated potent cytotoxicity specifically against EBV-positive tumor cell lines. In our in vivo xenograft model, administration of gp350-CAR-T cells resulted in significant inhibition of tumor growth, highlighting their capability to effectively target and eliminate EBV-positive lymphomas. This selectivity underscores the potential of utilizing gp350 as a specific target for immunotherapy. CONC...