Novel EBV LMP-2-affibody and affitoxin in molecular imaging and targeted therapy of nasopharyngeal carcinoma

English version

Autoři: Shanli Zhu ^aff001; Jun Chen ^aff001; Yirong Xiong ^aff001; Saidu Kamara ^aff001; Meiping Gu ^aff001; Wanlin Tang ^aff001; Shao Chen ^aff001; Haiyan Dong ^aff001; Xiangyang Xue ^aff001; Zhi-Ming Zheng ^aff002; Lifang Zhang ^aff001
Působiště autorů: Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, PR China ^aff001; Tumor Virus RNA Biology Section, RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland, United States of America ^aff002
Vyšlo v časopise: Novel EBV LMP-2-affibody and affitoxin in molecular imaging and targeted therapy of nasopharyngeal carcinoma. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008223
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008223

Souhrn

Epstein-Barr virus (EBV) infection is closely linked to several human malignancies including endemic Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinomas (NPC). Latent membrane protein 2 (LMP-2) of EBV plays a pivotal role in pathogenesis of EBV-related tumors and thus, is a potential target for diagnosis and targeted therapy of EBV LMP-2⁺ malignant cancers. Affibody molecules are developing as imaging probes and tumor-targeted delivery of small molecules. In this study, four EBV LMP-2-binding affibodies (Z_{EBV LMP-2}12, Z_{EBV LMP-2}132, Z_{EBV LMP-2}137, and Z_{EBV LMP-2}142) were identified by screening a phage-displayed LMP-2 peptide library for molecular imaging and targeted therapy in EBV xenograft mice model. Z_{EBV LMP-2} affibody has high binding affinity for EBV LMP-2 and accumulates in mouse tumor derived from EBV LMP-2⁺ xenografts for 24 h after intravenous (IV) injection. Subsequent fusion of Pseudomonas exotoxin PE38KDEL to the Z_{EBV LMP-2} 142 affibody led to production of Z142X affitoxin. This fused Z142X affitoxin exhibits high cytotoxicity specific for EBV⁺ cells in vitro and significant antitumor effect in mice bearing EBV⁺ tumor xenografts by IV injection. The data provide the proof of principle that EBV LMP-2-speicifc affibody molecules are useful for molecular imaging diagnosis and have potentials for targeted therapy of LMP-2-expressing EBV malignancies.

Klíčová slova:

Binding analysis – Cancer detection and diagnosis – Cell fusion – Cell staining – Cytotoxicity – Epstein-Barr virus – Nasopharyngeal carcinoma – Phage display

Zdroje

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