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.
Mol Cancer Ther. 2012 Mar;11(3):594-603. doi: 10.1158/1535-7163.MCT-11-0725. Epub 2011 Dec 14.
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.
鼻咽癌（NPC）是东南亚和中国癌症相关死亡的主要原因。转移和复发是 NPC 发病率和死亡率的主要原因。最近的证据表明， Epstein-Barr 病毒潜伏膜蛋白 1（LMP1）仅在大多数 NPC 中表达，是生物治疗的潜在靶点。在这项研究中，我们成功地制备了针对 LMP1 细胞外结构域的新型人抗体 Fab（HLEAFab），随后将其与丝裂霉素 C（MMC）缀合，从而形成免疫缀合物（HLEAFab-MMC）。检测了 HLEAFab-MMC 对 NPC 细胞系 HNE2/LMP1 的增殖和凋亡的影响以及对裸鼠 NPC 异种移植物生长的抑制率。在浓度为 200nmol/L 时，HLEAFab-MMC 对 HNE2/LMP1 细胞增殖的抑制率最高（76％），与 MMC（31％）和 HLEAFab（22％）相比，呈剂量依赖性。HNE2/LMP1 细胞系的凋亡率在 HLEAFab-MMC 组为 13.88％，MMC 组为 3.04％，HLEAFab 组为 2.78％，阴性对照组为 2.10％。在体内，HLEAFab-MMC 组裸鼠 NPC 异种移植物生长的抑制率为 55.1％，MMC 组为 26.5％，HLEAFab 组为 5.64％。综上所述，我们的研究结果表明，HLEAFab-MMC 是一种独特的免疫缀合物，有望成为治疗表达 LMP1 的 NPC 的新型治疗剂。
