EGFR 和 PD-L1 的多光谱荧光成像用于口腔鳞状细胞癌的精准检测：一项临床前和临床研究。
Multispectral fluorescence imaging of EGFR and PD-L1 for precision detection of oral squamous cell carcinoma: a preclinical and clinical study.
机构信息
Medical School of Chinese PLA, Beijing, 100853, China.
Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, China.
出版信息
BMC Med. 2024 Aug 26;22(1):342. doi: 10.1186/s12916-024-03559-w.
BACKGROUND
Early detection and treatment are effective methods for the management of oral squamous cell carcinoma (OSCC), which can be facilitated by the detection of tumor-specific OSCC biomarkers. The epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) are important therapeutic targets for OSCC. Multispectral fluorescence molecular imaging (FMI) can facilitate the detection of tumor multitarget expression with high sensitivity and safety. Hence, we developed Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes, in combination with multispectral FMI, to sensitively and noninvasively identify EGFR and PD-L1 expression for the detection and comprehensive treatment of OSCC.
METHODS
The expression of EGFR and PD-L1 was analyzed using bioinformatics data sources and specimens. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes were developed and tested on preclinical OSCC cell line and orthotopic OSCC mouse model, fresh OSCC patients' biopsied samples, and further clinical mouthwash trials were conducted in OSCC patients.
RESULTS
EGFR and PD-L1 were specifically expressed in human OSCC cell lines and tumor xenografts. Nimotuzumab-ICG and Atezolizumab-Cy5.5 imaging probes can specifically target to the tumor sites in an in situ human OSCC mouse model with good safety. The detection sensitivity and specificity of Nimotuzumab-ICG in patients were 96.4% and 100%, and 95.2% and 88.9% for Atezolizumab-Cy5.5.
CONCLUSIONS
EGFR and PD-L1 are highly expressed in OSCC, the combination of which is important for a precise prognosis of OSCC. EGFR and PD-L1 expression can be sensitively detected using the newly synthesized multispectral fluorescence imaging probes Nimotuzumab-ICG and Atezolizumab-Cy5.5, which can facilitate the sensitive and specific detection of OSCC and improve treatment outcomes.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR2100045738. Registered 23 April 2021, https://www.chictr.org.cn/bin/project/edit?pid=125220.
背景
早期检测和治疗是口腔鳞状细胞癌（OSCC）管理的有效方法，可以通过检测肿瘤特异性 OSCC 生物标志物来实现。表皮生长因子受体（EGFR）和程序性死亡配体 1（PD-L1）是 OSCC 的重要治疗靶点。多光谱荧光分子成像（FMI）可以高灵敏度和安全性促进肿瘤多靶点表达的检测。因此，我们开发了尼妥珠单抗-ICG 和阿特珠单抗-Cy5.5 成像探针，结合多光谱 FMI，以灵敏、无创的方式识别 EGFR 和 PD-L1 表达，用于 OSCC 的检测和综合治疗。
方法
使用生物信息学数据源和标本分析 EGFR 和 PD-L1 的表达。开发了尼妥珠单抗-ICG 和阿特珠单抗-Cy5.5 成像探针，并在临床前 OSCC 细胞系和原位 OSCC 小鼠模型、新鲜 OSCC 患者活检样本上进行了测试，并在 OSCC 患者中进一步进行了临床漱口试验。
结果
EGFR 和 PD-L1 在人 OSCC 细胞系和肿瘤异种移植中特异性表达。尼妥珠单抗-ICG 和阿特珠单抗-Cy5.5 成像探针可以特异性地靶向原位人 OSCC 小鼠模型中的肿瘤部位，具有良好的安全性。尼妥珠单抗-ICG 在患者中的检测灵敏度和特异性分别为 96.4%和 100%，阿特珠单抗-Cy5.5 分别为 95.2%和 88.9%。
结论
EGFR 和 PD-L1 在 OSCC 中高度表达，两者的结合对 OSCC 的精确预后很重要。新合成的多光谱荧光成像探针尼妥珠单抗-ICG 和阿特珠单抗-Cy5.5 可灵敏检测 EGFR 和 PD-L1 的表达，有助于敏感、特异性地检测 OSCC，并改善治疗效果。
试验注册
中国临床试验注册中心，ChiCTR2100045738。注册于 2021 年 4 月 23 日，https://www.chictr.org.cn/bin/project/edit?pid=125220。
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