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Characterization of human Fab antibody fragments specific to LMP1 (HLEAFab) in nasopharyngeal carcinoma for potential molecular diagnosis and therapeutic applications

机译:表征鼻咽癌中LMP1(HLEAFab)特异的人Fab抗体片段的潜在分子诊断和治疗应用

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摘要

In view of the previously demonstrated clinical role of the anti-latent membrane protein 1 (LMP1) immunoconjugate HLEAFab-MMC in the treatment of advanced nasopharyngeal carcinoma (NPC), reliable detection of LMP1 expression is of key importance. The aim of this study was to investigate LMP1 status in NPC. Tissue samples from 36 cases were analyzed by immunohistochemistry (IHC) and in situ hybridization for LMP1 and BNLF1 (LMP1 gene) expression, respectively. The results showed LMP1 expression in 20/36 (55.6%) cases in the HLEAFab group compared with 22/36 (61.1%) cases in the S12 group (purified mouse anti-human latent membrane protein 1 monoclonal antibody). The positive staining for LMP1 in the tumor cell membranes exhibited uniformity between HLEAFab and S12. BNLF1 was observed to be amplified in 19/36 NPC patients (52.8%). The sensitivities of HLEAFab-IHC-positivity and S12-IHC-positivity for amplification were 84.2 and 89.5%, respectively. Positive expression of LMP1 was present in a significant proportion of the NPC samples. The present findings provide an important strategy for molecular therapy targeting LMP1 in NPC patients.
机译:鉴于先前证实的抗潜伏膜蛋白1(LMP1)免疫缀合物HLEAFab-MMC在晚期鼻咽癌(NPC)的治疗中的临床作用,可靠检测LMP1表达至关重要。本研究的目的是调查LPC1在NPC中的状态。通过免疫组织化学(IHC)和原位杂交分析了36例患者的组织样品中LMP1和BNLF1(LMP1基因)的表达。结果显示,HLEAFab组中LMP1的表达为20/36(55.6%),而S12组中的LMP1表达为22/36(61.1%)(纯化的小鼠抗人潜伏膜蛋白1单克隆抗体)。肿瘤细胞膜中LMP1的阳性染色在HLEAFab和S12之间表现出均匀性。在19/36 NPC患者中观察到BNLF1扩增(52.8%)。 HLEAFab-IHC-阳性和S12-IHC-阳性的扩增敏感性分别为84.2和89.5%。 LMP1的阳性表达存在于相当大比例的NPC样品中。本发现为NPC患者靶向LMP1的分子治疗提供了重要策略。

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