Document Detail


A human Fab-based immunoconjugate specific for the LMP1 extracellular domain inhibits nasopharyngeal carcinoma growth in vitro and in vivo.
MedLine Citation:
PMID:  22169768     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Nasopharyngeal carcinoma (NPC) is a major cause of cancer-related death in Southeast Asia and in China. Metastasis and relapse are the primary cause of morbidity and mortality in NPC. Recent evidence suggests that the EBV Latent Membrane Protein 1 (LMP1) is almost exclusively expressed in all NPC and is a potential target for bio-therapy. In this study, we successfully prepared a novel human antibody Fab (HLEAFab) agaisnt 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 mouse were examined. The inhibition rate of HNE2/LMP1 cell proliferation was the highest for HLEAFab-MMC (76%) compared with MMC (31%) and HLEAFab (22%) (P < 0.05) 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 mouse was 55.1% in HLEAFab-MMC group, 26.5% in MMC group and 5.64% in HLEAFab group (P < 0.05). In summary, our findings demonstrate that HLEAFab-MMC is a unique immunoconjugate with potentials as a novel therapeutic agent in the treatment of LMP1-expressing NPC.
Authors:
Chen Renjie; Zhang Dawei; Mao Yuan; Zhu Jin; Ming Hao; Wen Juan; Ma Jun; Cao Qing; Lin Hong; Tang Qi; Liang Jie; Feng Zhenqing
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-14
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  -     ISSN:  1538-8514     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Nanjing medical university, The Key Laboratory of Antibody Technique of Ministry of Health, Nanjing medical university.
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