title: A neutralized human LMP1-IgG inhibits ENKTL growth by suppressing the JAK3/STAT3 signaling pathway.
abstract: Latent membrane protein 1 (LMP1), which is associated with the development of different types of Epstein-Barr virus (EBV) related lymphoma, has been suggested to be an important oncoprotein. In this study, a human anti-LMP1 IgG antibody (LMP1-IgG) was constructed and characterized by ELISA, western blotting (WB), affinity and immunohistochemistry (IHC) analyses. CCK-8, MTT, apoptosis assays, antibody-dependent cell-mediated cytotoxicity (ADCC) and CDC (complement-dependent cytotoxicity) assays were performed to evaluate the inhibitory effects of LMP1-IgG on extranodal nasal-type natural killer (NK)/T-cell lymphoma (ENKTL). Then, the influence of LMP1-IgG on the JAK/STAT signaling pathway was investigated. The results showed that the successfully constructed LMP1-IgG inhibited proliferation, induced apoptosis, and activated ADCC and CDC of ENKTL in a concentration- and time- dependent manner. Moreover, phosphorylation of JAK3 and STAT3 was inhibited by LMP1-IgG. Our data indicate that LMP1-IgG may provide a novel and promising therapeutic strategy for the treatment of LMP1-positive ENKTL.
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.|Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Weifei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China.
authors.forename: Siping
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Department of Pathology and The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Juqing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Hematology and Oncology, Department of Geriatric Lung Cancer Laboratory, Jiangsu Province Geriatric Hospital, Nanjing, China.
authors.forename: Suyao
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pathology, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Pathology, Jiangsu Cancer Hospital, Nanjing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, China.|The Fourth Clinical College of Nanjing Medical University, Nanjing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Yin
authors.affiliation: Huadong Medical Institute of Biotechniques, Nanjing, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D007150:Immunohistochemistry; D053616:Janus Kinase 3 / Q000378:metabolism*; D054391:Lymphoma, Extranodal NK-T-Cell / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007074:Immunoglobulin G; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014763:Viral Matrix Proteins; C507933:JAK3 protein, human; D053616:Janus Kinase 3
keywords: ENKTL; IgG; JAK/STAT; LMP1