Novel Bifunctional Affibody Molecules with Specific Binding to Both EBV LMP1 and LMP2 for Targeted Therapy of Nasopharyngeal Carcinoma

doi:10.3390/ijms241210126

科研成果详情

题名	Novel Bifunctional Affibody Molecules with Specific Binding to Both EBV LMP1 and LMP2 for Targeted Therapy of Nasopharyngeal Carcinoma
作者	Kamara, Saidu; Guo, Yanru; Wen, He; Liu, Ying; Liu, Lei; Zheng, Maolin; Zhang, Jing; Zhou, Luqi; Chen, Jun; Zhu, Shanli; Zhang, Lifang
发表日期	2023-06
发表期刊	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	affibody molecules nasopharyngeal carcinoma Epstein-Barr virus LMP1-LMP2 targeted therapy
其他关键词	EPSTEIN-BARR-VIRUS ; GROWTH-FACTOR RECEPTOR ; BISPECIFIC ANTIBODY ; PROTEINS ; EGFR ; ACTIVATION ; INDUCTION ; COMBINATION ; EXPRESSION ; FUSION
摘要	Antibodies are considered highly specific therapeutic agents in cancer medicines, and numerous formats have been developed. Among them, bispecific antibodies (BsAbs) have gained a lot of attention as a next-generation strategy for cancer therapy. However, poor tumor penetration is a major challenge because of their large size and thus contributes to suboptimal responses within cancer cells. On the other hand, affibody molecules are a new class of engineered affinity proteins and have achieved several promising results with their applications in molecular imaging diagnostics and targeted tumor therapy. In this study, an alternative format for bispecific molecules was constructed and investigated, named Z(LMP)110-277 and Z(LMP)277-110, that targets Epstein-Barr virus latent membrane protein 1 (LMP1) and latent membrane protein 2 (LMP2). Surface plasmon resonance (SPR), indirect immunofluorescence assay, co-immunoprecipitation, and near-infrared (NIR) imaging clearly demonstrated that Z(LMP)110-277 and Z(LMP)277-110 have good binding affinity and specificity for both LMP1 and LMP2 in vitro and in vivo. Moreover, Z(LMP)110-277 and Z(LMP)277-110, especially Z(LMP)277-110, significantly reduced the cell viability of C666-1 and CNE-2Z as compared to their monospecific counterparts. Z(LMP)110-277 and Z(LMP)277-110 could inhibit phosphorylation of proteins modulated by the MEK/ERK/p90RSK signaling pathway, ultimately leading to suppression of oncogene nuclear translocations. Furthermore, Z(LMP)110-277 and Z(LMP)277-110 showed significant antitumor efficacy in nasopharyngeal carcinoma-bearing nude mice. Overall, our results demonstrated that Z(LMP)110-277 and Z(LMP)277-110, especially Z(LMP)277-110, are promising novel prognostic indicators for molecular imaging and targeted tumor therapy of EBV-associated nasopharyngeal carcinoma.
资助项目	Zhejiang Provincial Basic Public Welfare Research Project[LY22H160015];National Nature Science Foundation of China[81972550 81372447]
出版者	MDPI
ISSN	1661-6596
EISSN	1422-0067
卷号	24 期号:12
DOI	10.3390/ijms241210126
页数	20
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Multidisciplinary
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry
WOS记录号	WOS:001015186000001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37373272
SCOPUSEID	2-s2.0-85163934459
通讯作者地址	[Zhang, Lifang]Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Catalysis;Molecular Biology;Spectroscopy;Computer Science Applications;Physical and Theoretical Chemistry;Organic Chemistry;Inorganic Chemistry
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/181095
专题	基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者	Zhang, Lifang
作者单位	Institute of Molecular Virology and Immunology,Department of Microbiology and Immunology,School of Basic Medical Sciences,Wenzhou Medical University,Wenzhou,325035,China
第一作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
通讯作者单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
第一作者的第一单位	基础医学院（机能实验教学中心）_病原生物学与免疫学系
推荐引用方式 GB/T 7714	Kamara, Saidu,Guo, Yanru,Wen, He,et al. Novel Bifunctional Affibody Molecules with Specific Binding to Both EBV LMP1 and LMP2 for Targeted Therapy of Nasopharyngeal Carcinoma[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2023,24(12).
APA	Kamara, Saidu., Guo, Yanru., Wen, He., Liu, Ying., Liu, Lei., ... & Zhang, Lifang. (2023). Novel Bifunctional Affibody Molecules with Specific Binding to Both EBV LMP1 and LMP2 for Targeted Therapy of Nasopharyngeal Carcinoma. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(12).
MLA	Kamara, Saidu,et al."Novel Bifunctional Affibody Molecules with Specific Binding to Both EBV LMP1 and LMP2 for Targeted Therapy of Nasopharyngeal Carcinoma".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 24.12(2023).