文章：

mAb14，一种针对细胞表面增殖细胞核抗原的单克隆抗体：用于塞扎里综合征诊断及靶向免疫治疗的潜在工具

mAb14, a Monoclonal Antibody against Cell Surface PCNA: A Potential Tool for Sezary Syndrome Diagnosis and Targeted Immunotherapy

原文发布日期：4 September 2023

DOI: 10.3390/cancers15174421

类型: Article

开放获取: 是

英文摘要：

Mycosis fungoides(MF) andSézary syndrome(SS) are the most common types of primary cutaneous T-cell lymphoma (CTCL). Proliferating cell nuclear antigen (PCNA) is expressed on the cell surface of cancer cells (csPCNA), but not on normal cells. It functions as an immune checkpoint ligand by interacting with natural killer (NK) cells through the NK inhibitory receptor NKp44, leading to the inhibition of NK cytotoxicity. A monoclonal antibody (mAb14) was established to detect csPCNA on cancer cells and block their interaction with NKp44. In this study, three CTCL cell lines and peripheral blood mononuclear cells (PBMCs) from patients with SS and healthy donors were analyzed for csPCNA using mAb14, compared to monoclonal antibody PC10, against nuclear PCNA (nPCNA). The following assays were used: immunostaining, imaging flow cytometry, flow cytometry, cell sorting, cell cycle analysis, ELISA, and the NK-cell cytotoxic assay. mAb14 successfully detected PCNA on the membrane and in the cytoplasm of viable CTCL cell lines associated with the G2/M phase. In the Sézary PBMCs, csPCNA was expressed on lymphoma cells that had an atypical morphology and not on normal cells. Furthermore, it was not expressed on PBMCs from healthy donors. In the co-culture of peripheral blood NK (pNK) cells with CTCL lines, mAb14 increased the secretion of IFN-γ, indicating the reactivation of pNK activity. However, mAb14 did not enhance the cytotoxic activity of pNK cells against CTCL cell lines. The unique expression of csPCNA detected by mAb14 suggests that csPCNA and mAb14 may serve as a potential biomarker and tool, respectively, for detecting malignant cells in SS and possibly other CTCL variants.

摘要翻译： 

蕈样肉芽肿（MF）与Sézary综合征（SS）是原发性皮肤T细胞淋巴瘤（CTCL）最常见的亚型。增殖细胞核抗原（PCNA）在癌细胞表面表达（csPCNA），但在正常细胞中不表达。其通过与自然杀伤（NK）细胞表面的抑制性受体NKp44相互作用，发挥免疫检查点配体功能，从而抑制NK细胞的细胞毒性。本研究制备了一种可特异性识别癌细胞表面PCNA并阻断其与NKp44相互作用的单克隆抗体（mAb14）。通过免疫染色、成像流式细胞术、流式细胞术、细胞分选、细胞周期分析、ELISA及NK细胞毒性实验，使用mAb14与针对核内PCNA（nPCNA）的单克隆抗体PC10，对三种CTCL细胞系及SS患者与健康供者外周血单个核细胞（PBMCs）的csPCNA表达进行对比分析。mAb14成功在处于G2/M期的活体CTCL细胞系膜表面及胞质中检测到PCNA。在Sézary综合征患者PBMCs中，csPCNA仅表达于形态学异常的淋巴瘤细胞，而不表达于正常细胞；健康供者PBMCs中未见表达。在外周血NK（pNK）细胞与CTCL细胞系的共培养实验中，mAb14能促进IFN-γ分泌，表明其可重新激活pNK细胞活性，但并未增强pNK细胞对CTCL细胞系的杀伤作用。mAb14检测到的csPCNA特异性表达模式提示，csPCNA及其对应抗体mAb14可能分别作为潜在生物标志物与检测工具，用于SS及其他CTCL亚型中恶性细胞的识别。

原文链接：

mAb14, a Monoclonal Antibody against Cell Surface PCNA: A Potential Tool for Sezary Syndrome Diagnosis and Targeted Immunotherapy