title: A human Fab-based immunoconjugate specific for the LMP1 extracellular domain inhibits nasopharyngeal carcinoma growth in vitro and in vivo.
abstract: Nasopharyngeal carcinoma (NPC) is a major cause of cancer-related death in Southeast Asia and China. Metastasis and relapse are the primary cause of morbidity and mortality in NPC. Recent evidence suggests that the Epstein-Barr virus latent membrane protein 1 (LMP1) is exclusively expressed in most NPC and is a potential target for biotherapy. In this study, we successfully prepared a novel human antibody Fab (HLEAFab) against LMP1 extracellular domain, which was subsequently conjugated with mitomycin C (MMC), thus forming an immunoconjugate (HLEAFab-MMC). The effects of HLEAFab-MMC on proliferation and apoptosis in NPC cell lines HNE2/LMP1 and the inhibition rate of growth of NPC xenografts in nude mice were examined. The inhibition rate of HNE2/LMP1 cell proliferation was the highest for HLEAFab-MMC (76%) compared with MMC (31%) and HLEAFab (22%) at a concentration of 200 nmol/L and showed dose-dependent fashion. The apoptosis rate of HNE2/LMP1 cell lines was 13.88% in HLEAFab-MMC group, 3.04% in MMC group, 2.78% in HLEAFab group, and 2.10% in negative control group at the same concentration, respectively. In vivo, the inhibition rate of growth of NPC xenografts in nude mice was 55.1% in HLEAFab-MMC group, 26.5% in MMC group, and 5.64% in HLEAFab group. In summary, our findings show that HLEAFab-MMC is a unique immunoconjugate with the potential as a novel therapeutic agent in the treatment of LMP1-expressing NPC.
authors.affiliation: Nanjing Medical University, The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center, The Key Laboratory of Antibody Technique of Ministry of Health and The Second Affiliated Hospital, Department of Otolaryngology Head and Neck Surgery, 140 Hanzhong Road, Nanjing 210029, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Chen
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Mao
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Ming
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Qing
authors.initials: Q
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites / Q000276:immunology; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use*; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000737:chemistry; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019151:Peptide Library; D047368:Tumor Burden / Q000187:drug effects; D014763:Viral Matrix Proteins / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; D014763:Viral Matrix Proteins; D016685:Mitomycin