Clinical evaluation of a novel-developed clone 3E2 for the detection of PD-L1 expression status in lung adenocarcinoma

对一种新型克隆3E2进行临床评价,用于检测肺腺癌中PD-L1表达状态

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Abstract

BACKGROUND: Detecting programmed death-ligand 1 (PD-L1) expression helps identify patients likely to respond to PD-1/PD-L1 therapies. However, the high costs of PD-L1 assays, such as SP263 pharmDx, limit their widespread use, creating a need for cost-effective alternatives. This study evaluates the analytical performance and concordance of the newly developed 3E2 PD-L1 antibody with established clones in lung adenocarcinoma (LUAD). METHODS: The 3E2 monoclonal antibody was developed using the hybridoma technique. Its performance was compared with that of the SP263, Cell Signaling Technology (CST) E1L3N, and Abcam 28-8 clones using immunohistochemistry on 101 LUAD samples. Concordance was assessed using Bland-Altman plots, confusion matrices, and quantitative analyses. Survival analysis was performed to investigate the correlation between PD-L1 expression detected by the 3E2 clone and treatment outcomes in patients undergoing immunotherapy. RESULTS: Among 30 PD-L1 monoclonal antibodies generated via hybridoma, the 3E2 clone showed high sensitivity and specificity for PD-L1 detection. It exhibited strong concordance with Abcam 28-8 in positive (placenta) and negative (normal stomach mucosa) control tissues, as well as non-small cell lung cancer and melanoma samples (accuracy: 90.1%, κ: 0.797). Moderate agreement was observed with CST E1L3N (accuracy: 69.8%, κ: 0.401) and SP263 (accuracy: 55.4%, κ: 0.262), with higher PD-L1 expression detected by E1L3N and SP263. Bland-Altman analysis showed minimal bias between 3E2 and 28-8. Survival analysis revealed that patients with PD-L1 expression ≥ 5% (detected by 3E2) had significantly better outcomes (p = 0.021). CONCLUSIONS: The 3E2 antibody demonstrates high concordance with Abcam 28-8, offering a potential cost-effective alternative for PD-L1 detection with preliminary prognostic value in immunotherapy-treated LUAD patients. Further validation is required to confirm its clinical utility.

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