Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy
Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, with a five-year survival rate below 15 %. Claudin 18.2 (CLDN18.2) has emerged as a novel potential therapeutic target in PDAC. Zolbetuximab, a monoclonal antibody targeting CLDN18.2, has demonstrated therapeutic benefit in gastric cance...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-05-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000932 |
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| author | Riley J. Arseneau Emma Kempster Carley Bekkers Thomas Samson Boris L. Gala-Lopez Ravi Ramjeesingh Jeanette E. Boudreau Thomas Arnason |
| author_facet | Riley J. Arseneau Emma Kempster Carley Bekkers Thomas Samson Boris L. Gala-Lopez Ravi Ramjeesingh Jeanette E. Boudreau Thomas Arnason |
| author_sort | Riley J. Arseneau |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, with a five-year survival rate below 15 %. Claudin 18.2 (CLDN18.2) has emerged as a novel potential therapeutic target in PDAC. Zolbetuximab, a monoclonal antibody targeting CLDN18.2, has demonstrated therapeutic benefit in gastric cancers and is now in phase 2 clinical trials for PDAC. Trial eligibility for zolbetuximab requires tumor membranous immunohistochemical staining with the pan-claudin 18 companion diagnostic antibody clone 43–14A. However, the expression of CLDN18 detected using this clone has only been evaluated in 62 patients from a single retrospective study. Herein, we report immunohistochemical staining using 43–14A on surgically resected PDAC samples (n = 120). Samples were stained following the protocol used in clinical trials, using the 43–14A VENTANA antibody in a prediluted kit, and according to the manufacturer's recommended protocol. Positive cases were defined as ≥ 75 % of tumor cells exhibiting membranous staining with an intensity of ≥ 2+. Out of 120 PDAC cases, 39 (32.5 %) stained positive for CLDN18 with 43–14A. A significant association was observed between lower tumor grade and higher 43–14A staining (p < 0.05). CLDN18-positive cases demonstrated significantly improved survival at the cohort's median overall survival (23 months, p < 0.05), suggesting that claudin expression could serve as a both a diagnostic and prognostic marker. Our findings indicate that 32.5 % of PDAC tumors in this cohort are positive for CLDN18, suggesting that a significant proportion of patients with PDAC could benefit from zolbetuximab and other CLDN18.2 targeted immunotherapies if pancreatic cancer therapeutic trials prove successful. |
| format | Article |
| id | doaj-art-52ca5bfca9bf4d3c820aac62ea48e714 |
| institution | DOAJ |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-52ca5bfca9bf4d3c820aac62ea48e7142025-08-20T03:03:27ZengElsevierTranslational Oncology1936-52332025-05-015510236210.1016/j.tranon.2025.102362Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapyRiley J. Arseneau0Emma Kempster1Carley Bekkers2Thomas Samson3Boris L. Gala-Lopez4Ravi Ramjeesingh5Jeanette E. Boudreau6Thomas Arnason7Department of Pathology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, CanadaNova Scotia Health, Halifax, NS, CanadaNova Scotia Health, Halifax, NS, CanadaNova Scotia Health, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, Canada; Department of Microbiology & Immunology, Dalhousie University, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, Canada; Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, Canada; Department of Microbiology & Immunology, Dalhousie University, NS, CanadaDepartment of Pathology, Dalhousie University, Halifax, NS, Canada; Nova Scotia Health, Halifax, NS, Canada; Corresponding author.Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, with a five-year survival rate below 15 %. Claudin 18.2 (CLDN18.2) has emerged as a novel potential therapeutic target in PDAC. Zolbetuximab, a monoclonal antibody targeting CLDN18.2, has demonstrated therapeutic benefit in gastric cancers and is now in phase 2 clinical trials for PDAC. Trial eligibility for zolbetuximab requires tumor membranous immunohistochemical staining with the pan-claudin 18 companion diagnostic antibody clone 43–14A. However, the expression of CLDN18 detected using this clone has only been evaluated in 62 patients from a single retrospective study. Herein, we report immunohistochemical staining using 43–14A on surgically resected PDAC samples (n = 120). Samples were stained following the protocol used in clinical trials, using the 43–14A VENTANA antibody in a prediluted kit, and according to the manufacturer's recommended protocol. Positive cases were defined as ≥ 75 % of tumor cells exhibiting membranous staining with an intensity of ≥ 2+. Out of 120 PDAC cases, 39 (32.5 %) stained positive for CLDN18 with 43–14A. A significant association was observed between lower tumor grade and higher 43–14A staining (p < 0.05). CLDN18-positive cases demonstrated significantly improved survival at the cohort's median overall survival (23 months, p < 0.05), suggesting that claudin expression could serve as a both a diagnostic and prognostic marker. Our findings indicate that 32.5 % of PDAC tumors in this cohort are positive for CLDN18, suggesting that a significant proportion of patients with PDAC could benefit from zolbetuximab and other CLDN18.2 targeted immunotherapies if pancreatic cancer therapeutic trials prove successful.http://www.sciencedirect.com/science/article/pii/S1936523325000932Pancreatic ductal carcinomaImmunohistochemistryClaudin 18 protein, humanBiomarkers43–14azolbetuximab |
| spellingShingle | Riley J. Arseneau Emma Kempster Carley Bekkers Thomas Samson Boris L. Gala-Lopez Ravi Ramjeesingh Jeanette E. Boudreau Thomas Arnason Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy Translational Oncology Pancreatic ductal carcinoma Immunohistochemistry Claudin 18 protein, human Biomarkers 43–14a zolbetuximab |
| title | Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy |
| title_full | Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy |
| title_fullStr | Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy |
| title_full_unstemmed | Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy |
| title_short | Claudin 18 (43–14A clone) expression in pancreatic ductal adenocarcinoma: Assessment of a potential clinical biomarker for zolbetuximab therapy |
| title_sort | claudin 18 43 14a clone expression in pancreatic ductal adenocarcinoma assessment of a potential clinical biomarker for zolbetuximab therapy |
| topic | Pancreatic ductal carcinoma Immunohistochemistry Claudin 18 protein, human Biomarkers 43–14a zolbetuximab |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000932 |
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