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

Abstract 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. Conclusion Our findings advocate for the clinical application of gp350-directed CAR-T therapy as a prospective treatment strategy for patients with relapsed or refractory EBV-positive tumors. Given the encouraging preclinical results, further research is warranted to optimize CAR-T cell production processes and extend the potential of this therapy to other EBV-associated malignancies, paving the way for improved outcomes in affected patient populations.