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 mecha...
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BMC
2025-02-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06188-w |
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| author | Jiajia Wang Huiping Wang Yangyang Ding Nengneng Cao Fengya Nan Fan Wu Cong Li Xue Liang Meng Xiao Jinjing Guo Zhimai Gao Li Yan Tielin Zhou Yanli Li Zhimin Zhai |
| author_facet | Jiajia Wang Huiping Wang Yangyang Ding Nengneng Cao Fengya Nan Fan Wu Cong Li Xue Liang Meng Xiao Jinjing Guo Zhimai Gao Li Yan Tielin Zhou Yanli Li Zhimin Zhai |
| author_sort | Jiajia Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-a6b3ca771b314104ae5cd417ad3a363a |
| institution | DOAJ |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-a6b3ca771b314104ae5cd417ad3a363a2025-08-20T02:43:16ZengBMCJournal of Translational Medicine1479-58762025-02-0123111510.1186/s12967-025-06188-wGp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-TJiajia Wang0Huiping Wang1Yangyang Ding2Nengneng Cao3Fengya Nan4Fan Wu5Cong Li6Xue Liang7Meng Xiao8Jinjing Guo9Zhimai Gao10Li Yan11Tielin Zhou12Yanli Li13Zhimin Zhai14Department of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Pathology, Department of Pathology, Anhui Medical University, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityZENO Biotechnology (Shenzhen) CoDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityZeno Therapeutics Pte. Ltd.Department of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology/Hematologic Diseases Research Center, The Second Affiliated Hospital of Anhui Medical UniversityAbstract 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.https://doi.org/10.1186/s12967-025-06188-wCAR-T target researchGp350EBVBurkitt lymphomaImmunotherapy |
| spellingShingle | Jiajia Wang Huiping Wang Yangyang Ding Nengneng Cao Fengya Nan Fan Wu Cong Li Xue Liang Meng Xiao Jinjing Guo Zhimai Gao Li Yan Tielin Zhou Yanli Li Zhimin Zhai Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T Journal of Translational Medicine CAR-T target research Gp350 EBV Burkitt lymphoma Immunotherapy |
| title | Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T |
| title_full | Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T |
| title_fullStr | Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T |
| title_full_unstemmed | Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T |
| title_short | Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T |
| title_sort | gp350 targeted car t therapy in ebv positive burkitt lymphoma pre clinical development of gp350 car t |
| topic | CAR-T target research Gp350 EBV Burkitt lymphoma Immunotherapy |
| url | https://doi.org/10.1186/s12967-025-06188-w |
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