Journal Article

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

Kamara, Saidu, Zhu, Shanli, Tang, Wanlin, Xue, Xiangyang, Chen, Jun, Zheng, Zhi-Ming, Chen, Shao, Zhang, Lifang, Gu, Meiping, Xiong, Yirong, Dong, Haiyan

2020

Overview

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 (ZEBV LMP-212, ZEBV LMP-2132, ZEBV LMP-2137, and ZEBV LMP-2142) were identified by screening a phage-displayed LMP-2 peptide library for molecular imaging and targeted therapy in EBV xenograft mice model. ZEBV 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 ZEBV 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amino acids / Animals / Anticancer properties / Antigens / Antitumor activity / Binding / Biology and life sciences / Burkitt's lymphoma / Cell cycle / Cell Line, Tumor / Cloning / Cytotoxicity / Diagnosis / Drug Delivery Systems / Epidermal growth factor / Epstein-Barr virus / Exotoxins / Female / Gene expression / Genomes / Herpesvirus 4, Human / Humans / Imaging / Immunology / Immunotoxins - metabolism / Immunotoxins - therapeutic use / Infections / Injection / Intravenous administration / Kinases / LMP2 protein / Lymphoma / Medicine and health sciences / Membrane proteins / Mice / Mice, Inbred BALB C / Molecular Imaging / Molecular weight / Nasopharyngeal carcinoma / Nasopharyngeal Carcinoma - diagnostic imaging / Nasopharyngeal Carcinoma - therapy / Nasopharyngeal Carcinoma - virology / Nasopharyngeal Neoplasms - diagnostic imaging / Nasopharyngeal Neoplasms - therapy / Nasopharyngeal Neoplasms - virology / Neoplasms, Experimental - diagnostic imaging / Neoplasms, Experimental - therapy / Pathogenesis / Peptide Library / Phages / Protein Binding / Proteins / Research and Analysis Methods / Supervision / Therapy / Throat cancer / Toxicity / Tumors / Viral Matrix Proteins - antagonists & inhibitors / Viral Matrix Proteins - metabolism / Virology / Viruses / Xenograft Model Antitumor Assays / Xenografts / Xenotransplantation