CD30检测方法与协同药物组合的综合分析，以优化淋巴瘤中维布妥昔单抗的治疗

Integrated analysis of CD30 detection methodologies and synergistic drug combinations for optimizing brentuximab vedotin therapy in lymphoma.

作者信息

Ye Mingyu, Wang Tao, Song Zhiqiang, Liu Xuefei, Liu Ping, Zhang Ling, Tang Gusheng, He Miaoxia, Liu Na, Yang Jianmin

机构信息

Department of Hematology, Institute of Hematology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.

Department of Pathology, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.

出版信息

Clin Exp Med. 2025 Jun 27;25(1):221. doi: 10.1007/s10238-025-01765-1.

DOI:10.1007/s10238-025-01765-1

PMID:40576820

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12204884/

Abstract

Brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate, has shown significant efficacy in CD30-positive lymphoma. However, the relationships between CD30 expression levels and BV efficacy remains unclear. In this study, we first evaluated the reliability of CD30 detection by immunohistochemistry (IHC) and found that flow cytometry (FCM) offers higher sensitivity and accuracy in assessing CD30 expression. Therefore, FCM may serve as a more effective method for evaluating CD30 levels. Furthermore, we confirmed a positive correlation between CD30 expression levels and BV efficacy. However, even when BV was applied to tumor cells with 100% CD30 expression, its anti-tumor activity did not reach complete eradication, highlighting the need for synergistic combination therapies. To address this, we conducted high-throughput screening (HTS) and identified auranofin and napabucasin as synergistic agents that enhance the efficacy of BV. These findings not only highlight the advantages of FCM for CD30 detection, but also provide valuable insights into combination strategies to optimize the therapeutic potential of BV.

摘要

本妥昔单抗（BV）是一种靶向CD30的抗体药物偶联物，已在CD30阳性淋巴瘤中显示出显著疗效。然而，CD30表达水平与BV疗效之间的关系仍不清楚。在本研究中，我们首先评估了免疫组织化学（IHC）检测CD30的可靠性，发现流式细胞术（FCM）在评估CD30表达方面具有更高的灵敏度和准确性。因此，FCM可能是评估CD30水平更有效的方法。此外，我们证实了CD30表达水平与BV疗效之间存在正相关。然而，即使将BV应用于CD30表达率为100%的肿瘤细胞，其抗肿瘤活性也未达到完全根除，这突出了协同联合治疗的必要性。为了解决这一问题，我们进行了高通量筛选（HTS），并确定金诺芬和萘布卡星为增强BV疗效的协同剂。这些发现不仅突出了FCM在检测CD30方面的优势，还为优化BV治疗潜力的联合策略提供了有价值的见解。